The term ‘brain fog’ is something that many of us are familiar with these days. But what does it actually mean? And why does it happen?
While not a technical term as such, ‘brain fog’ is how most people describe having difficulty concentrating or thinking clearly, forgetfulness, and general mental fatigue.
There can be many reasons for these brain function issues, particularly stress, lack of sleep, poor diet, and certain medications. Many of these things can be modified by making changes to our lifestyles and health regimes.
However, it’s also possible to support and enhance our short- and long-term brain function with specific nutrients - particularly those from Methyl-Life®.
If you’re searching for expert information on how to improve brain health, you’re in the right place. This article will explain the factors involved in healthy cognitive function and the nutrients shown to help with thinking, remembering, and processing information. We will also discuss the benefits of supplements for brain health from Methyl-Life®.
Understanding brain health
The brain makes up only 2% of total body weight but consumes around 20% of daily energy. [1] It needs an enormous range of nutrients to function properly, particularly nutrients that help in transferring energy to neurons and supporting membrane integrity.
Understanding the importance of certain foods for brain health is essential for supporting mental fitness. Studies show that specific nutrients have significant impact on neuronal function, synaptic plasticity, and cognitive ability. [2] Substances that regulate synaptic plasticity (such as choline and phosphatidylserine) also play important roles in neurological processes. Research has also highlighted the link between highly processed foods and brain health decline. [3]
Two of the most crucial nutrients for brain health are also the nutrients that a large proportion of the population is lacking: folate and vitamin B12.
Those with a mutation on the MTHFR gene are at risk of reduced folate and B12 levels, which can then lead to higher homocysteine levels and lower S-adenosylmethionine (SAM). [4] In the brain, SAMe is essential for the production of healthy neurotransmitters and amino acids in brain tissues. Numerous studies show that MTHFR mutations can lead to impairments in cognitive and motor function. The cerebellum and hippocampus are particularly susceptible to poor MTHFR function. The cerebellum has the highest levels of homocysteine, which makes it more vulnerable to damage via homocysteine and reduced levels of dopamine, serotonin and amino acids, specifically glutamate and GABA. [5] The cerebellum is involved in coordinating a wide range of functions and processes in the brain and comprises more than half of the body’s neurons.
Elevated homocysteine also increases risk factors such as including oxidative stress, amyloid β aggregation, tau phosphorylation, and dysfunction of the vascular system. [6] These factors are associated with cognitive decline and the early signs of Alzheimer's disease, such as synaptic impairment, neuronal dysfunction and formation of neurofibrillary tangles. [7]
Introduction to Methyl-Life®
Methyl-Life® is a US-based nutraceutical company dedicated to cognitive health. As experts in MTHFR, methylation, and nervous system function, Methyl-Life® provides both information and highly specialized nutritional supplements to support mind and body.
Methyl-Life® is a recognized authority on brain health assessment, particularly regarding methylation and MTHFR-related polymorphisms. Their mission is to empower those struggling with health challenges through their evidence-based guides, nutrition, and wellness support.
Every product in the Methyl-Life® range has been formulated according to scientific research and analysis. This is to ensure a truly therapeutic and effective result.
How Methyl-Life® supplements support focus
Methyl-Life® has invested in scientific research and expertise to create a unique and powerful range of brain health supplements.
Methylfolate
L-methylfolate is the natural and highly bioavailable form of folate. It is the predominant form that occurs naturally in the body and used in numerous biological processes. It is also the only form of folate that can bypass the MTHFR mutation. [8]
L-methylfolate is required for numerous functions of the brain and nervous system, including:
• Proper methylation [9]
• Synthesis and repair of DNA/RNA [10]
• Conversion of homocysteine to methionine for cardiovascular health [11]
• Production of vital neurotransmitters for healthy mood [12]
• Nervous system maintenance [13]
• Normal fetal growth and development and prevention of congenital abnormalities [14]
• Immune system maintenance [15
• Healthy myelin formation [16]
• Daily energy production
… and many other enzymatic reactions involved in amino acid synthesis and vitamin metabolism.
Methyl-Life’s® range of methyfolate supplements include dosages 15mg, 10mg, 7.5mg+B12, 5mg, 3mg+B12, and 2.5mg.
All Methyl-Life® methylfolate products are made with a calcium salt form of (6S)-5-methyltetrahydrofolate (or L-5-MTHF), tested to be the most potent and pure methylfolate in the market today.
Vitamin B12
Hydroxocobalamin is a highly bioavailable form of B12 recommended over cyanocobalamin for vitamin B12 deficiency. [17] It is the precursor of methylcobalamin and adenosylcobalamin (active forms of vitamin B12) and essential for DNA and amino acid synthesis, fatty acid metabolism, and nerve maintenance. [18] Vitamin B12 is vital for the synthesis of neurotransmitters for healthy mood and cognitive function. [19]
Supplements for enhancing memory recall
https://gem-3910432.netCiticoline
Citicoline is a naturally occurring form of choline which is required for making phosphatidylcholine, the structural phospholipid of cell membranes. Citicoline is able to pass through the blood–brain barrier (BBB) and integrate with the membrane and phospholipids where it assists in membrane integrity, brain activity, and enhances the functions of various brain messengers. [20]
Citicoline is shown to increase levels of mood regulators (serotonin, dopamine and norepinephrine) in the central nervous system, which contributes to neuroprotection, [21] Supplementation has been shown to improve cognitive function, learning, and working memory and also protects against oxidative stress. [22]
Citicoline is shown to improve overall memory performance and may help protect against memory loss in older adults. [23]
Phosphatidylserine
Phosphatidylserine is a major membrane lipid that makes up around 13–15% of the phospholipids in the cerebral cortex. [24] It covers and protects brain cells, improving the speed and efficiency of transmitting messages within the brain.
Supplementation with phosphatidylserine is shown to enhance cognitive functions such as memory and possibly even reduce the deterioration of nerve cells, potentially reducing the risk of cognitive decline. [25] It’s also shown to improve mood and relaxation before and after mental stress. [26]
Pyrroloquinoline quinone
Pyrroloquinoline quinone (PQQ) is a natural enzyme found in fruits, vegetables, and breast milk. It helps to protect the brain cells and mitochondria (the energy producers of cells) from oxidative stress by increasing nerve growth factor (NGF) and NGF receptors. [27] PQQ boosts brain power by increasing blood flow and oxygen in the decision-making part of your brain, called the right prefrontal cortex. Research suggests that PQQ is effective in enhancing memory, attention, judgment, and cognitive function. [28]
These three “brain enhancers” are all included in Methyl-Life’s® Focus & Recall. This one-of-a-kind brain health formula contains Citicoline, Phosphatidylserine, and PQQ to support memory, learning, mood, and attention white protecting neurons from mental and physical stress.
Magtein L-threonate
Magtein® L-Threonate is a form of magnesium shown in clinical studies to be effective in enhancing memory, attention and learning focus.
The brain requires magnesium for nerve signal transmission and supporting the integrity of membranes. [29]
Enhancing magnesium concentration in the brain is shown to enhance both short-term synaptic function and improve learning and memory. [30]
Unlike other forms of magnesium, Magtein® can cross both the blood-brain and blood-CSF barriers and deliver magnesium directly to brain cells. In a study involving elderly adults, those taking Magtein® showed significant improvement in learning, recall, memory, and overall cognitive abilities. [31]
Methyl-Life’s® Magtein® L-Threonate Magnesium is a revolutionary magnesium supplement to optimize brain function and support long-term cognitive health.
Safety and dosage recommendations
All Methyl-Life® products have been clinically tested for safety. No adverse effects have been reported with any ingredients used in our products.
However, it’s always important to speak with a healthcare practitioner before starting any supplement regime, especially if you have other medical conditions or concerns.
The takeaway
Your brain is central to every thought, memory, movement, and emotion. It is your intelligence, sense interpreter, motor function, and grand controller.
Maintaining brain health throughout life is essential for preserving mental and cognitive function.
In addition to standard health protocols such as a nutritious daily diet and regular exercise, it’s both possible and advisable to support brain health with supplementary nutrients. This is especially important for those who are at risk of nutritional deficiencies.
Methyl-Life® offers the ultimate support for optimizing brain health through education, supplements, and genuine compassion.
References
1. https://www.ncbi.nlm.nih.gov/books/NBK20367
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805706/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879751/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750636/
6. https://www.frontiersin.org/articles/10.3389/fnins.2021.778123/full
7. https://pubmed.ncbi.nlm.nih.gov/32812023
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564482/
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262611/
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262611/
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026708/
12. https://onlinelibrary.wiley.com/doi/full/10.1111/cns.13207
13. https://www.ncbi.nlm.nih.gov/books/NBK557632/#
14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540/
15. https://i.trade-cloud.com.cn/upload/6405/file/20210929/english-version-magnafolate-enhancing-immunity_524485.pdf
16. https://pubmed.ncbi.nlm.nih.gov/15896807/
17. https://www.bmj.com/content/349/bmj.g5389
18. https://www.ncbi.nlm.nih.gov/books/NBK557632/#
19. https://onlinelibrary.wiley.com/doi/full/10.1111/cns.13207
20. https://pubmed.ncbi.nlm.nih.gov/17171187
21. https://pubmed.ncbi.nlm.nih.gov/28417449/
22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878037/
23. https://www.sciencedirect.com/science/article/pii/S002231662200267X
24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258547/
25. https://pubmed.ncbi.nlm.nih.gov/25933483/
26. https://pubmed.ncbi.nlm.nih.gov/18616866/
27. https://pubmed.ncbi.nlm.nih.gov/27526146/
28. https://pubmed.ncbi.nlm.nih.gov/34415830/
29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820677
30. https://pubmed.ncbi.nlm.nih.gov/20152124/
31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786204/
Updated On: November 20, 2023
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Breast cancer is one of the most common forms of cancer worldwide and the second leading cause of cancer-related death among women after lung cancer. [1] Although every woman is at some risk for breast cancer, the degree of risk for individual women can vary considerably.
Research suggests that genes are the strongest hereditary risk factor for developing breast cancer, particularly in women who are affected at a younger age. In fact, around 10–20% of early-onset cases are hereditary. [2]
For this reason, women with a family history of breast cancer are strongly advised to be aware of their higher risks and seek regular checkups.
This article will discuss the role of genetic factors in breast cancer, including the potential for the MTHFR gene to play a part. We will also cover how to manage your risks and support your health if you are affected by certain gene variants.
Breast cancer: An overview:
Breast cancer accounts for about 12.5% of all new cancer cases worldwide and around 30% of all new cancer cases in women each year in the US. [3] About 13% of women will develop breast cancer some time during their lives.
In 2020, there were an estimated 2.3 million new cancer cases and 685,000 cancer deaths (1 in 6 deaths) worldwide. An estimated 2,964,197 new female breast cancer cases are expected to occur in 2040 - a 31% increase from today. [4]
The most common symptoms of breast cancer include a lump in the breast (75% of women diagnosed), a change in shape and size of the breast (57%), a lump under the armpit (56%), and pain in one breast (56%).
While the main risk factors for breast cancer include getting older and being a woman, many other factors are now known to be involved. Hormonal factors can increase the risk, including the age at which a woman starts menstruating and the density of her breasts throughout her lifetime. Previous cancer treatment may also increase the risk. However, genetic factors are also a significant contributor.
Approximately 70% of women who develop breast cancer have cancerous tissue that has receptors for estrogen and/or progesterone. This is a form of cancer called hormone receptor-positive. Both estrogen and progesterone are related to cancer cell growth and spread. [5] Studies have shown that women with a family history of breast cancer are more likely to have ER (estrogen receptors) and PR (progesterone receptor) tumors than women without a family history. [6]
Connection between genes and breast cancer risk
Some studies suggest that first-degree relatives of individuals with breast cancer have triple the risk of developing cancer themselves. [7] Other studies indicate that up to 10% of all breast cancer cases are linked to genetic factors. In women aged under 30, genetic factors may account for up to 25% of cases. BRCA1 and BRCA2 are the 2 most important genes responsible for increased breast cancer susceptibility. [8]
People who inherit harmful variants in the genes BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) have increased risks of breast cancer and tend to develop cancer at younger ages than people who do not have these variants. However, studies suggest that around 55–72% of women with the BRCA1 mutation and 45–69% of women with the BRCA2 mutation will develop breast cancer before they turn 70. [9]
More recently, research has indicated a relationship between the MTHFR polymorphisms and the increased risk of breast cancer.
What is the MTHFR gene?
The MTHFR gene is involved in numerous essential processes within the body, including regulating folate levels, DNA synthesis, methylation, and tumorigenesis. [10] The MTHFR gene is also responsible for producing MTHFR, an enzyme that catalyzes and converts folic acid to methylfolate.
The MTHFR enzyme is vital for proper folate metabolism and DNA biosynthesis, methylation, and repairing actively dividing cells. However, a common mutation - known as a SNP (single nucleotide polymorphisms) - often occurs in the MTHFR gene. There are two common variants of the MTHFR gene and of the two, the C677T variation is believed to play a role in the development of breast cancer.
Approximately 25% of the world’s population carries MTHFR C677T, some populations carry higher percentages, including 47% of Hispanics, 36% of Europeans, and 30% of East Asians. [11]
Poor function of the MTHFR enzyme leads to reduced levels of methylfolate, which in turn results in a lack of folate synthesis and DNA repair. Changes in the patterns of DNA methylation can lead to genetic faults - or mutations - that can then contribute to the process of carcinogenesis. [12]
Research has linked low folate levels and folate-related polymorphisms such as MTHFR to the incidence of cancer. [13] MTHFR polymorphisms have also been shown to influence the risk of breast cancer, with several studies showing a higher risk of incidence of breast cancer in individuals with MTHFR. [14] This appears to be more prevalent in Caucasian and Asian populations.
The MTHFR C677T mutation appears to increase the risk of both breast cancer and ovarian cancer, especially among Asian women.
Women with active ovulatory cycles who also have MTHFR gene mutations are most at risk for breast cancer. [15] However, scientists are not yet certain if the mutation itself causes cancer, or if it simply increases the risk by reducing methylfolate and/or glutathione to defend against cancer cells, or other factors. Further research is pending.
Prevention and awareness
Many factors contribute to the development of breast cancer, and include both environmental and genetic factors. The most common of these are age, diet, body mass index (BMI), reproductive history, common oncogenes, breast density, and family history. [16] However, research suggests that many risks can be modified, particularly diet, exercise; avoiding smoking, alcohol and drugs, and supporting healthy hormonal balance. [17]
Tips on breast cancer prevention
Diet
Obesity has been linked to many cancers, including breast cancer. [18]
Eating a diet rich in antioxidants - particularly Vitamin C and vitamin E - can help protect against breast cancer risk. Vitamin E has been shown to reduce the number of carcinogen-induced mammary tumors in animals. [19] Recommended diets include the DASH diet and the Mediterranean diet, which are rich in vegetables, fruits, fish, whole grains, and unsaturated fats from nuts and extra-virgin olive oil. [20]
Supporting your folate levels by eating plenty of folate-rich foods can also help support healthy cell repair in the body. For additional support, consider supplementing with methylfolate, active B12, and other nutrients required by the body for proper methylation and DNA synthesis.
Exercise
Numerous studies have reported the importance of physical activity in preventing breast cancer. Women can reduce their risk of developing cancer by 25–30% if they exercise regularly. Being active also helps in recovering from breast cancer, both during and after treatment. [21]
While any amount of exercise is beneficial, most studies recommend at least 30-60 min/day five days a week. This can include brisk walking, running, swimming, cycling, or any other activity that increases the heart rate.
Awareness of family history
Family history is one of the most well-known factors in the development of breast cancer. Around 5–10% of women diagnosed have a family member who has also had breast cancer. [22]
Faulty genes can increase the risk of breast cancer. Normally, the BRCA1 and BRCA2 genes stop cells in the body from growing and dividing out of control. However, a mutation on the gene can lead to cells multiplying and developing into various cancers, including breast cancer.
BRCA1 mutations occur in around 7% of families with a history of breast cancer, while BRCA2 mutations are found in about 20% of families at high risk for both breast and ovarian cancers. [23]
Anyone who has a family history of breast cancer or is concerned that they may have a harmful BRCA1 or BRCA2 gene should speak to their healthcare provider. Testing can identify risk factors for potential gene variants
The role of regular screening and mammograms
While no test is 100% accurate, regular mammograms can reduce the risk of dying from breast cancer. Early detection of breast cancer may mean more efficient treatment and less time spent recovering. [24]
Self-examination is also an important and effective means of prevention. Regularly checking your breasts will help you identify any changes or abnormalities such as lumps or skin changes. You can then report any changes to your healthcare provider right away.
The takeaway
While every woman is at risk for developing breast cancer, there are ways to reduce that risk - even when genetic links are present.
The first step is to be aware of your risk. If you have relatives who have had any form of cancer or any other genetic mutations - including the MTHFR mutation - it’s essential that you monitor your own health throughout life. Have regular checkups. This includes both mammograms and self-examinations. Maintain a healthy lifestyle with a nutritious diet, regular exercise, and limiting harmful factors such as alcohol and smoking.
When in doubt, consult a qualified healthcare practitioner.
References
1. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21583
2. https://pubmed.ncbi.nlm.nih.gov/33807872/
3. https://www.wcrf.org/cancer-trends/worldwide-cancer-data/
4. https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.10528
5. https://www.ncbi.nlm.nih.gov/books/NBK22312/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253097
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059326/
8. https://www.ncbi.nlm.nih.gov/books/NBK482286/
9. https://pubmed.ncbi.nlm.nih.gov/28632866/
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270429/
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630484/
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073588/
13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073588
14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073588/
15. https://pubmed.ncbi.nlm.nih.gov/12602921/
16. https://pubmed.ncbi.nlm.nih.gov/28152151/
17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939980/
18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857053
19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939980/
20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8839871
21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076351
22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973811/
23. https://www.ncbi.nlm.nih.gov/books/NBK470239
24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214657/
Updated On: November 20, 2023
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Research into the relationship between gut health and its effects on brain function has grown significantly in recent years. Scientists are now aware that the “gut-brain axis” (GBA) has an important impact on wellbeing. The gut-brain axis is a link between the brain and the gastrointestinal (GI) system, which includes the enteric nervous system and the diverse microbiome.
This article will discuss the gut-brain axis and its role in parts of the brain and their functions. We will also explain how improving gut health may have a role in the treatment and prevention of mental health disorders.
What is the gut-brain axis?
The gut-brain axis is the two-way communication path between the gut and the brain. [1] This communication pathway occurs via the vagus nerve, the largest nerve in the body. By communicating this way, the gut can directly influence our brain function and behavior, and vice versa. This is because the gut-brain network includes the central nervous system, the autonomic nervous system (ANS), the enteric nervous system (ENS), the hypothalamic pituitary adrenal (HPA) axis, and brain and spinal cord. [2]
While essential for normal gut function, this intricate communication system has many effects on behavior, including mood, motivation, and other cognitive functions. [3] Many hormones and neurotransmitters are made in the gut, including gamma-aminobutyric acid (GABA), dopamine, serotonin, and substances produced as a result of fermentation, such as short-chain fatty acids (SCFA). [4]
How Gut Health Affects Mood and Behavior
Gut microbiota has a major influence on gut-brain interaction. More recent research has shown that the gut–brain axis enables gut microbiota to communicate with the brain through direct and indirect signaling pathways to influence brain physiology, function, and even behavior. [5]
Studies have linked dysbiosis and functional gastrointestinal disorders with many central nervous disorders such as autism, anxiety, and depression. [6]
The gut microbiota is a complex ecosystem comprising billions of bacteria. Gut microbiota benefits the body in a number of ways, starting with digestion. Bacteria break down complex carbohydrates and proteins from food to produce substances that are important for numerous bodily functions. Microbial communities within the gut change in composition, diversity, and activity throughout life, which also impacts behavior and cognition. [7]
Probiotics and their role in brain health
Probiotics are live organisms that include bacteria and yeast and can be taken as gut health supplements. Probiotics support the health and function of the gut, which in turn can provide significant health benefits to overall wellbeing. [8]
Research suggests that probiotics can support healthy brain function and mood by enhancing the quantity and quality of gut bacteria. Several neurotransmitters including serotonin, GABA (gamma-aminobutyric acid), and glutamate are produced in the gut. In fact, around 50% of dopamine and 95% of serotonin is produced in the gastrointestinal tract. In addition,
the hypothalamic-pituitary-adrenal (HPA) axis is believed to be activated when gut microbiota is disrupted, leading to both inflammatory diseases and mental health disorders. There is also evidence that depression and inflammatory gut conditions occur due to poor gut health and poor diet. [9] A lack of mood-supporting neurotransmitters is associated with anxiety and depressive symptoms. [10]
Good sources of probiotics include fermented products such as yogurt, kefir, miso, tempeh, sauerkraut, sourdough products, kimchi, olives, and pickles. [11]
Probiotic supplements are an effective and convenient means of supporting gut microbiome. Probiotics are reported to reduce symptoms of depression as well as reducing C-reactive protein concentrations, suggesting their promising effects in treating depressive symptoms. [12]
Other studies have shown probiotics to have a positive effect on the gut-brain axis and mental well-being, particularly in improving mood and reducing depressive symptoms. These results demonstrate the close relationship between microbiome balance and psychological parameters, and how targeted supplementation can positively influence the gut-brain axis for improved mental wellness.
Looking for the best probiotic for gut health? Methyl-Life’s® Gut Health 4 in 1 is a full-spectrum gut health supplement to enhance microbiome health and gut barrier function. It contains prebiotics, probiotics, short-chain fatty acids, and digestive enzymes to reduce digestive inflammation and support the growth of beneficial gut bacteria. Another option - especially for those taking antibiotics - is Methyl-Life’s® RestorFlora, a spore-based probiotic that contains the beneficial yeast saccharomyces boulardii to support and regenerate gut bacteria.
Gut inflammation and its impact on the brain
Just as the brain can influence intestinal function, gut inflammation can influence mood, cognitive function, and mental health. Numerous studies have revealed a link between inflammatory bowel diseases (IBDs) and neurodegenerative diseases, particularly inflammatory bowel disease (IBD), which is closely linked to mental health disorders. [13]
Harmful gut bacteria can trigger an immune response, which then increases the inflammatory processes that break down the gut barrier and activate pain sensory pathways in the gut and the enteric nervous system. [14]
Enteric dysbiosis - an imbalance in the gut bacteria - can lead to substances from the inflamed intestines passing through the intestinal barriers into the brain. Inflammatory mediators in the gut can also cause changes in the structure and function of the central nervous system (CNS). Dysregulation of intestinal microbiota can damage the intestinal epithelial barrier leading to intestinal inflammation and sends harmful proteins from the enteric nervous system to the brain. This can not only cause further gastrointestinal dysfunction but further inflammation in the brain affecting neuroplasticity, potentially increasing the risk of diseases such as Parkinson’s. [15] Studies have also highlighted the contribution of the gut microbiota to peripheral inflammation in multiple sclerosis (MS). [16]
How to improve gut health
The intestinal barrier requires a wide range of beneficial bacteria to maintain its strength and development. Gut bacteria provide energy in the form of short-chain fatty acids and also by releasing antimicrobial substances to inhibit pathogens.
The best gut health foods are those rich in fiber and prebiotics. A lack of fiber in the diet results in the thinning of the epithelial layer. High saturated fats and simple sugars also impair intestinal barrier integrity by reducing tight junctions and allowing the growth of harmful bacteria.
Sources of fiber include whole grains (barley, oats, brown rice, wheat), fruits, nuts, root vegetables, legumes, pulses.
How to improve gut health
The intestinal barrier requires a wide range of beneficial bacteria to maintain its strength and development. Gut bacteria provide energy in the form of short-chain fatty acids and also by releasing antimicrobial substances to inhibit pathogens. [17]
The best gut health foods are those rich in fiber and prebiotics. A lack of fiber in the diet results in the thinning of the epithelial layer. High saturated fats and simple sugars also impair intestinal barrier integrity by reducing tight junctions and allowing the growth of harmful bacteria. [18]
Sources of fiber include whole grains (barley, oats, brown rice, wheat), fruits, nuts, root vegetables, legumes, pulses. [19]
Prebiotics are carbohydrates that are fermented by the gut microbiome to produce therapeutic and health-promoting compounds. These compounds can strengthen probiotic bacteria and function as a ‘fuel’. [20] Good sources of prebiotics include asparagus, sugar beet, garlic, chicory, onion, yogurt, cheese, Jerusalem artichoke, green bananas, soybean, peas, beans. [21]
Signs your gut may be affecting your brain
Different gut bacteria can result in different symptoms of mood disorders. A lack of healthy gut microbiota is associated with depression, anxiety, stress, and personality changes. [22]
Various internet sources claim that other symptoms may include difficulty sleeping, poor concentration, poor memory, and ‘brain fog’.
If you are experiencing these symptoms on a regular basis and they are affecting your daily life, it’s important to seek help from a qualified healthcare practitioner and perhaps consider a gut health test.
The takeaway
The gut-brain axis is a bidirectional communication system between the gut and the brain, and disruptions in the gut microbiota can significantly impact mental health and mood. However, improving the gut microbiome with a nutritious diet, prebiotics, and probiotics can reduce the inflammatory processes in the gut and brain that are linked to these mood symptoms. Check out Methyl-Life’s® comprehensive guides to improving gut health and supporting cognitive function
References
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748575/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234057/
5. https://www.mdpi.com/2072-6643/14/3/568
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/
7. https://www.mdpi.com/2072-6643/14/3/568
8. https://pubmed.ncbi.nlm.nih.gov/24290962/
9. https://pubmed.ncbi.nlm.nih.gov/32983670/
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337499/
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837740
12. https://pubmed.ncbi.nlm.nih.gov/26706022/
13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396333/
14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469458/
15. https://www.frontiersin.org/articles/10.3389/fneur.2023.1185375/full
16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396333/
17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455721
18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455721/
19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614039/
20. https://www.frontiersin.org/articles/10.3389/fnut.2023.1173660/full
21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463098/#sec3-foods-08-00092title
22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987167/
Updated On: October 20, 2023
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Did you know that nearly 5% of the world’s population currently struggles with ADHD?
There are many reasons for the rise in ADHD diagnoses over the past few years, and those affected face a number of challenges. Acknowledging the complexities of this behavioral disorder can help reduce the stigma and misconceptions.
Attention Deficit Hyperactivity Disorder (ADHD) affects an estimated 5-7% of children and 2.5-6.7% of adults worldwide. [1] ADHD in children is highest in the US, where prevalence is around 8.7%. [2]
The recent rise in cases of ADHD in adults has raised concerns about overdiagnosis and overprescription of stimulant medications. While diagnosis criteria have broadened over the years, so too has awareness of the condition in previously underrepresented groups such as women.
This article will discuss the characteristics of ADHD and its associated conditions. We will also cover the options for management and treatment.
What is ADHD?
ADHD is a neurodevelopmental disorder that affects an individual’s ability to function. ADHD characteristics include inattentiveness, hyperactivity, and/or impulsivity. Although Attention Deficit Hyperactivity Disorder was originally distinct from Attention Deficit Disorder, the DSM IV (Diagnostic and Statistical Manual of Mental Disorders) has now combined this into one disorder with three subtypes: primarily hyperactive and impulsive, primarily inattentive, and combined.
People with ADHD show a persistent pattern of inattention and/or hyperactivity–impulsivity. The ADHD diagnosis criteria for a youth (aged up to 17) includes having at least six of the nine symptoms mentioned in DSM 5, while an adult must show five or more symptoms. These symptoms must have been present for at least 6 months on a regular basis.
Inattentive ADHD symptoms include: [3]
• Lack of attention to detail; making careless mistakes in schoolwork, work, or other activities.
• Inability to listen or follow instructions; failing to finish tasks (i.e. losing focus or being distracted).
• Avoiding or being reluctant to do tasks that require mental effort over a long period of time (such as schoolwork or homework).
• Losing items such as keys, paperwork, phone.
Hyperactive ADHD symptoms include:
• Lack of attention to detail; making careless mistakes in schoolwork, work, or other activities.
• Inability to listen or follow instructions; failing to finish tasks (i.e. losing focus or being distracted).
• Avoiding or being reluctant to do tasks that require mental effort over a long period of time (such as schoolwork or homework).
• Losing items such as keys, paperwork, phone.
Hyperactive ADHD symptoms include:
• Fidgeting, squirming when seated; leaving their seat; highly restless
• Being unable to play or take part in leisure activities quietly
• Behaving as if “driven by an internal motor”
• Talking excessively or interrupting others who are speaking
• Unable to wait their turn
Individuals must also have displayed several inattentive or hyperactive-impulsive symptoms before age 12, and these symptoms must have been present in at least two settings (e.g., home, school, work; with friends or relatives). These symptoms must have interfered with their quality of life in some way, and are not related to another mental disorder (such as a mood disorder or personality disorder).
The importance of ADHD awareness
While ADHD has certainly become more commonplace in recent years, there are still many misunderstandings about the disorder. Increasing ADHD awareness can help reduce the stigma directed at those who have been diagnosed, and improve their access to support.
Common misconceptions include:
• ADHD is not a real condition
Over 10,000 scientific studies have been published on ADHD. It impairs normal life for millions of people. It also has genetic links, which indicate it is indeed a ‘real’ disorder.
• Only boys have ADHD
The male-female ratio of diagnosis of ADHD in childhood is 4:1. In adults, the ratio is now around 1:1. [4] This suggests that ADHD in girls does exist but is often overlooked and therefore underdiagnosed.
• You can outgrow ADHD
Research suggests that ADHD is a lifetime disorder. Up to 90% of children diagnosed will continue to experience symptoms into adulthood. One study suggests that around 75% of adults currently with ADHD were not previously diagnosed in childhood. [5]
• ADHD is just poor parenting
Many studies indicate that ADHD most often involves genetic and neurological factors. These may include pregnancy complications, brain damage, toxins, and infections rather than social factors. [6]
Co-existing conditions: an overview
It’s estimated that around 60-100% of children with ADHD also have at least one other condition that persists into adulthood. [7] These typically include learning disorders, depression, and behavior problems. Up to 80% of adults with ADHD have at least one coexisting psychiatric disorder, such as a mood and anxiety disorder, substance use disorder, and/or personality disorder. [8]
• Social phobias may be the most common coexisting condition, at 29.3%. Adults with ADHD also may have bipolar disorder (19.4%), major depressive disorder (18.6%), and generalized anxiety disorder (8.0%). [9]
• Learning disorders
Studies suggest that up to 92% of children diagnosed with ADHD also have a learning disorder. [10] Learning disorders in writing are twice as common (65%) than in reading, math, or spelling. [11]
• Depressive disorders
Childhood ADHD is associated with an increased risk of recurrent depression in young adults. [12] One study suggests that depression in youth with ADHD is around 12-50%, which is more than five times higher than in youth without ADHD. [13]
• Anxiety disorders
The risk for anxiety disorders is higher in people with ADHD than in the general population, with rates estimated at around 50%. [14]
One study reported that 28% of individuals referred to a tertiary clinic for mood and anxiety assessment were found to have undetected ADHD. [15]
Coexisting conditions can mask ADHD symptoms, which make it difficult to detect or manage ADHD. The nonspecific nature of ADHD symptoms can overlap with other psychiatric disorders, complicating diagnosis. Clinicians need to understand the patient’s range of symptoms and behavioral history.
Managing ADHD
The availability of effective ADHD treatments has improved significantly in recent years. Treatments are designed to target and alleviate the core symptoms of ADHD and functional impairment and can be either pharmacological or non-pharmacological. [16]
Pharmacological methods (medications) [17]
• Stimulant drugs: Norepinephrine and dopamine reuptake inhibitors
• Non-stimulant drugs:
- Alpha2 adrenergic receptor agonists (guanfacine, clonidine)
- Selective noradrenaline reuptake inhibitor (atomoxetine)
ADHD medication is one of the most commonly prescribed medication classes in child and adolescent psychiatry. A qualitative systematic review of studies regarding the benefits of ADHD medication has suggested there may be some short-term improvements in educational outcomes and in behavior, including fewer injuries and accidents. [18]
Non-pharmacological methods
Psychosocial interventions for ADHD include behavioral parent training (BPT), behavioral classroom interventions, and skills training. Studies suggest that these have benefits for children with ADHD, particularly for improving overall functioning.
BPT is the most well-studied and supported method. It involves teaching parents effective ways of coping with their child’s behavior, such as building a positive parent-child relationship, encouraging good behavior with incentive systems, and implementing appropriate consequences for bad behavior. [19]
Nutritive support: ADHD and diet or supplements
Folate (vitamin B9)
Folate is crucial for numerous biochemical pathways including neural stem cell development and neurotransmitter synthesis. [20] Lack of folate has often been linked to cognitive deficit, and studies have suggested that genetic variants affecting folate metabolism may be linked to ADHD.
Supporting folate levels with methylfolate, the most bioavailable form of folate, may be an option for those with ADHD.
Nootropics
Preliminary evidence also suggests that nootropics such as phosphatidylserine may be effective for reducing symptoms of inattention in children with ADHD. [21] Another important nootropic, citicoline, has also been found to improve attention and psychomotor speed and reduce impulsivity. [22]
ADHD management and support
If you’re a parent of a child with ADHD, some strategies for managing behavior may include:
• Establish a structured daily schedule that includes regular meal times, homework, play, and sleep.
• Break tasks into simple steps and provide clear instructions.
• Keep them active by encouraging daily physical exercise. This can boost endorphin release which then improves focus and reduces impulsivity.
• Minimize distractions in study and play areas to improve focus and concentration, supporting their ability to complete tasks and engage in social interactions.
• Work with teachers, counselors, and ADHD support groups to develop an individualized plan that supports your child’s specific needs.
• Seek help from health professionals regarding medication, ADHD therapy, and/or nutritional needs.
Managing your own ADHD symptoms
• Establish a daily routine into a schedule that covers all of your activities and tasks.
• Break tasks down into smaller, more manageable steps. Use a detailed checklist to create a step-by-step roadmap.
• Minimize distractions by decluttering and simplifying your surroundings at home or in the workplace. This can help improve focus.
• Be aware of your limits and recognize when you need to remove tasks from your plate.
• Seek help from health professionals regarding medication, behavioral therapies, and/or nutritional needs.
The takeaway
As research into ADHD continues, it’s important to keep an open mind about the disorder and those affected by it. Greater understanding of how it can impact someone’s life - and the lives of others - can help reduce the stigma.
If you or someone you love has been diagnosed with ADHD, take the time to think about what changes you can make to help minimize symptoms. Living with ADHD can be managed with the right medications, behavioral therapies, nutritional interventions, and simply organizing your daily life and surroundings. And be sure to check out Methyl-Life® for more ADHD resources and information.
References
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616454
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616454/
3. https://www.cdc.gov/ncbddd/adhd/diagnosis.html
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616454
5. https://pubmed.ncbi.nlm.nih.gov/15197048/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927422/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745333/
8. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-017-1463-3
9. https://pubmed.ncbi.nlm.nih.gov/16585449/
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745333/
11. https://pubmed.ncbi.nlm.nih.gov/15495544/
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381237/
13. https://pubmed.ncbi.nlm.nih.gov/10102726/
14. https://pubmed.ncbi.nlm.nih.gov/16585449/
15. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-017-1463-3
16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713849/
17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713849/
18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697582/
19. https://link.springer.com/article/10.1007/s40474-014-0034-2
20. https://pubmed.ncbi.nlm.nih.gov/29407547/
21. https://pubmed.ncbi.nlm.nih.gov/33539192/
22. https://pubmed.ncbi.nlm.nih.gov/26179181
Updated On: November 17, 2023
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We humans have been taking supplements for almost 200 years - and we’re hooked.
In 2022, the global nutritional supplements market was worth an estimated US 167.94 billion. While the pandemic certainly fuelled a recent surge, our demand for supplements is expected to continue, with the market predicted to hit USD 301.41 billion by 2030.
While the supplement industry is governed by various statutes and regulations, concerns have recently been raised over the lack of FDA (Food and Drug Administration) guidance regarding levels of impurities or other byproducts, which may increase the risk of misbranding.
When it comes to nutritional supplementation, consumers rely almost solely on product labels to make informed decisions. So, it may be a shock to learn that not all labels tell the truth.
This article will discuss everything you need to know about the role of the FDA, dietary supplement misbranding, and how to choose supplements that are 100% guaranteed safe.
What is misbranding?
Misbranding occurs when supplement labels provide false, misleading, or insufficient information about the product contents. According to the FDA, a dietary supplement is mislabeled if:
• The label or advertising material is false or misleading.
• The label doesn’t list the name and/or quantity of each ingredient supplemented, meaning that the consumer may be ingesting ingredients they would otherwise avoid.
• The label doesn’t include the words “dietary supplement” (or an acceptable equivalent).
• The product contains an herb or other botanical and fails to identify from which part of the plant it is derived.
• The product fails to meet required standards of identity, strength, quality, purity, or compositional specifications.
Adulteration is slightly different. Adulteration, by definition, occurs when products are found to be contaminated, defective, unsafe, not shown to be safe, dirty, produced under insanitary conditions, and/or manufactured under procedures and controls that do not comply with cGMP (current Good Manufacturing Practices) regulations.
Supplement misbranding has been an issue for as long as supplements and adulterated drugs have existed. Unfortunately, with the industry growing at such a rapid pace, the scale of potential harm is larger than ever.
Misbranding may not always be deliberate. But whether deliberate or not, the implications are vast.
At its most serious, incorrect labeling may pose grave health risks to the consumer. Users may be exposed to allergens or other ingredients they would normally avoid due to health conditions or interactions with other medications. They may also end up taking higher-than-expected dosages of certain ingredients, which can also have serious risks.
The Dietary Supplement Health and Education Act (DSHEA) provides a clear definition of dietary supplements as food, not drugs. This definition serves as the foundation for how they are labeled and marketed. However, despite efforts by authorities to regulate and oversee supplement labeling, the vastness of the market makes it a mammoth task.
Repeated instances of misbranding can erode consumer trust in the industry as a whole, pushing potential users away from taking “honest” supplements for health.
At the very least, consumers certainly do not want to pay more for a product they believe is of higher quality or efficacy based on misleading label information.
Types of dietary supplement misbranding
Supplement misbranding can take various forms. Some of the most common examples include:
Incorrect identification of ingredients
Selling a product under a name that doesn't correspond to its actual content. For example, selling a supplement named "St. John's Wort" that contains an entirely different herb.
Misleading labels
Using labels that overstate the benefits of the supplement - for example, claiming that the product can "cure" or "treat" certain medical conditions, but without the scientific evidence to prove it. Supplements (dietary or otherwise) cannot claim to diagnose, treat, cure, or prevent a disease unless they have been evaluated and approved by the FDA to do so.
Wrongly claiming the source or origin of the supplement (for example, claiming that an ingredient is organic or from a certain country) is also misleading.
Incorrect dosing information
The label does not accurately reflect the concentration of the ingredients, potentially leading to overdosing or underdosing.
In other cases, the label may fail to provide necessary warnings about potential side effects, interactions with other drugs, or risks associated with the ingredients.
Omission of ingredients
Not listing all ingredients present in the nutrient supplement. This is especially dangerous for consumers with allergies or those taking medication that may adversely interact with undisclosed ingredients.
Falsifying supplement certification
Using symbols or badges indicating third-party certification or testing when the product hasn't been certified or tested by those organizations.
Concealing information
Using extremely small fonts or hidden panels to provide crucial information, making it difficult for the average consumer to find or read.
Role of FDA in regulating dietary supplements
The U.S. Food and Drug Administration is responsible for regulating dietary supplements to ensure consumer safety and fair marketing practices. It regulates both finished products and their ingredients, and all supplements are subject to a different set of regulations than those covering "conventional" foods and drug products.
This involves:
• inspecting manufacturing establishments
• reviewing new dietary ingredient (NDI) notifications and other submissions for supplements
• investigating consumer complaints and reviewing adverse event reports from firms, consumers, and healthcare providers to identify products that may be unsafe
• monitoring the supplement marketplace
• examining products and ingredients offered for import to determine whether they meet U.S. requirements.
While the FDA doesn’t actually approve dietary supplements or their labeling, they may review and authorize the claims made by supplement manufacturers.
The FDA does not approve dietary supplements for safety and effectiveness as it is not authorized to do so. In fact, supplements can be produced and marketed without notifying the FDA at all. The only situation in which companies must submit a premarket safety notification to the FDA is if the product contains “new dietary ingredients” (i.e., ingredients that were not marketed in the U.S. before October 1994).
Besides searching for the supplements FDA approved list, consumers are wholly dependent on the company’s adherence to Current Good Manufacturing Practices (CGMPs). CGMP refers to the Current Good Manufacturing Practice for regulations enforced by the FDA. CGMP regulates the manufacturing, packaging, and holding operations of supplements to ensure their identity, purity, quality, strength, and composition. These supplement regulations are designed to prevent adulteration and misbranding of the products.
Methyl-Life® and FDA
Here at Methyl-Life®, we’re not only FDA-registered and audited but wholly committed to CGMP. This is evident in our rigorous testing, quality control, and adherence to standardized procedures during manufacturing, packaging, and distribution. It’s why all of our products are on the FDA approved supplements list, and why we’re one of the world’s most trusted methylfolate supplement manufacturers.
Methyl-Life®’s commitment to the quality and safety of all ingredients begins with our thorough evaluation of a supplier’s credentials and certifications. We only work with manufacturers who are NSF-certified (National Sanitation Foundation). This is the highest level of assurance that a product has not only gone through the specified standard operating procedures strictly guided by the FDA, but that it has exceeded those standards and can be verified by a trusted independent organization. NSF certification ensures every aspect of a product's development is thoroughly evaluated; a requirement that goes well beyond that of the FDA’s.
Also unlike FDA requirements, NSF certification means products are continuously re-tested and manufacturing facilities are subject to regular inspections.
All of Methyl-Life®'s suppliers must be able to show that they are compliant with manufacturing regulatory standards. They must also have proven track records in delivering quality ingredients. All ingredients used in our formulas have extensive and detailed paperwork that is required and delivered for each batch ordered (the product manufacturer files these documents for traceability). No ingredient is received or used in any finished product for Methyl-Life® without this paperwork. Examples of some traceability documents include: ingredient source statements, flow charts of the ingredient’s production/source, handling and storing specifications, certificate of analysis (e.g., USP standards regarding how each ingredient is to be tested and what is “passable” vs. “unacceptable”), allergen details, testing results for contaminants, pesticides, and heavy metals, Material Safety Data Sheet (MSDS), and any other relevant certifications (i.e. halal, kosher, non-GMO, etc.).
This dedication to quality underpins our stringent measures to maximize the safety, efficacy, and reliability of our products. Not only that, Methyl-Life® offers comprehensive information and education to help customers better understand which supplements may be most suitable for their health.
The takeaway
Nutrient supplementation should always be approached with caution. However, avoiding misbranded products can be as simple as checking the product label and researching the company. When choosing a supplement, check that it adheres to CGMP regulations and has the relevant certifications and approvals. It may also be helpful to check both the FDA-approved list of supplements and the FDA banned supplements list.
NSF certification demonstrates that a brand has exercised due diligence in meeting the strictest requirements for quality, compliance and safety.
Methyl-Life®’s tireless commitment to customer safety is reflected in our robust quality assurance practices. We will continue to uphold the integrity of the US supplement industry and empower consumers to make informed choices about their health and well-being.
Updated On: October 2, 2023
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The events of the past few years have seen people all over the world seek out new and better ways to optimize their health. Since 2020, sales of dietary supplements and nutraceuticals have soared. [1]
Consequently, the role of quality assurance practices by supplement manufacturers has never been more important.
When comparing supplement brands, there are several important factors to consider. Along with reputation, cost, and valid research, a major indicator of efficacy is a brand’s quality assurance practices.
In the US, supplements are not rigorously regulated as pharmaceutical drugs. This makes robust quality management systems even more crucial.
That’s where Methyl-Life® excels. Our dedication to customer satisfaction underpins our stringent measures to maximize the safety, efficacy, and reliability of our products.
First, let’s explain the difference between quality assurance vs quality control.
What is quality assurance?
Quality assurance focuses on processes and systems implemented to ensure the overall quality of supplement manufacturing. It involves establishing guidelines, procedures, and standards to prevent defects and ensure consistency in the final product.
What is quality control?
Quality control involves inspecting and testing specific samples during production to identify and address any deviations from the established standards.
So, how do we do it?
Our commitment to quality
As one of the world’s best-known methylfolate supplement manufacturers, Methyl-Life® is 100% dedicated to the Good Manufacturing Practices (GMP) set by the US Food and Drug Administration (FDA). These practices encompass rigorous testing, quality control, and adherence to standardized procedures during manufacturing, packaging, and distribution.
Before we work with a supplier, we conduct a thorough evaluation of their credentials and certifications. We ensure they are compliant with regulatory standards and have proven track records in delivering quality ingredients.
This assessment provides us with the transparency we need to be fully informed about the origins of our ingredients and production processes. It is imperative that every single component of our products meets the required quality benchmarks so that we can stand behind our promise to customers. We also strive to minimize the risk of harmful substances or impurities being present in our ingredients so that we can fully safeguard consumer health.
Every ingredient we use in our products undergoes third-party testing to confirm that it matches every detail on the Certificate of Analysis. If any ingredient doesn't meet the standard COA, we don't use it.
Our determination to provide only the best is what led us to Cerebrofolate™. Cerebrofolate™ is an exclusive, patented methylfolate that has been tested in a recent study as the most potent methylfolate in the world.
Cerebrofolate™ is superior to other L-methylfolates for many reasons. It’s a crystalline (Type I) calcium salt form of (6S)-5-methyltetrahydrofolate (or L-5-MTHF) and comprises >=80% “free methylfolate”. Other forms of methylfolate (such as L-5-MTHF, glucosamine) comprise only ~52% or less of “free methylfolate”.
In addition, Cerebrofolate™ is produced in a CGMP facility which is FDA-registered and audited, FSSC22000, kosher, halal, and ISO9001 certified. FSSC22000 represents the highest level of
quality and certification for ingredients used in dietary supplements. And, while most companies employ skip-batch testing (testing once every determined number of batches), every single batch of Cerebrofolate™ is tested for impurities, heavy metals, potency and purity.
Unsurprisingly, Cerebrofolate™ has been shown to retain its stability for up to two years when stored at room temperature.
These factors make Cerebrofolate™ not only one of the purest but also the most potent methylfolate on the market today, which is why we’ve chosen it as our primary ingredient.
Technological proficiency
Our laboratory technicians apply strict testing procedures throughout our manufacturing process so that all of our products meet - or even exceed - industry standards.
This includes sophisticated analytical techniques to identify and quantify individual compounds within a supplement. This allows us to verify the potency and purity of active ingredients.
We also test for potential contaminants to ascertain that the supplement contains the intended ingredients without any unexpected or harmful substances.
Our stability testing involves subjecting our products to various environmental conditions (such as temperature, light and humidity) to assess their shelf life and ensure every supplement remains effective and safe over time.
Certifications and compliance
Methyl-Life’s® compliance with rigorous guidelines are reflected in our certifications and registration. We are FDA registered and audited, use NSF certified manufacturers, and follow cGMP best practices.
We implement stringent quality control measures at every stage of the manufacturing process. We are committed to ensuring that our finished products meet the required standards of purity, strength, and composition.
Our cGMP best practices are followed to ensure that our facility adheres to FDA regulations and has passed all audits for quality control. The cGMP is essentially an FDA-recommended baseline for all supplement manufacturers as it proves we have the right safety practices in place to control risks and hazards. Third-party independent assessment confirms these safety practices and processes.
Most importantly, the majority of our manufacturers are NSF certified.
Methyl-Life® meets these criteria:
• Hygiene standards
Methyl-Life® manufacturing facilities maintain a high level of cleanliness and sanitation to prevent cross-contamination and ensure the integrity of our products.
• Trained personnel
We employ trained and qualified personnel who understand cGMP principles and follow the procedures to maintain product quality and safety. Our employees receive regular training on cGMP principles, safety protocols, and quality standards to uphold a culture of excellence and compliance.
• Documentation
All of our manufacturing processes, including equipment calibration, testing, and product formulations, are fully documented for traceability and accountability.
• Raw material testing
All raw materials used in Methyl-Life® supplements undergo thorough testing to ascertain their purity and potency. These stringent quality checks allow us to identify and prevent potential contamination, adulteration, or mislabeling of products.
• Third-party testing
Every product developed by the manufacturer has its own Certificate of Analysis based on post-production testing. In addition, every batch is also third-party tested for potency at an independent lab to ensure the results are consistent.
• NSF certification
NSF certification is the highest assurance that a product has been tested by a trusted independent certification organization. This certification is well beyond FDA requirements as it ensures every aspect of a product's development is thoroughly evaluated. NSF certification is not a one-off: it involves regular re-testing of products alongside on-site inspections of manufacturing facilities.
• Batch testing (NOT skip-batch testing)
Each batch of finished products undergoes testing to verify its compliance with quality standards before being released for distribution. Many companies only employ skip-batch testing (i.e., batches are tested at random). At Methyl-Life®, we test every batch, we believe our consumers deserve the very best. This ensures that our consumers receive products with accurate ingredient lists, appropriate potency, and minimal risk of harmful impurities.
• Environmental control
Our manufacturing facility is equipped with environmental controls to maintain conditions such as temperature and humidity, preventing sensitive ingredients from degradation.
• Supplier verification
We conduct regular audits and verification of our every supplier to establish their adherence to cGMP principles and the quality of their raw materials.
• Customer services
Methyl-Life® puts every customer first. We address every query and question promptly and thoroughly to provide a resolution as quickly as possible.
Evolving through feedback
Methyl-Life® takes feedback seriously. We actively encourage our customers to share their experiences with our products and services. This information contributes to our continuous improvement and our relentless pursuit of excellence. It also allows us to address any concerns. We’re always looking for ways to improve or exceed our customers’ expectations!
Our website includes several options for customers to contact us, including an inquiry form. Our internal support team is available via email, and live chat. We do not outsource our customer support to any contractors or third-party companies: our customer support is entirely in-house.
We get many questions from our customers regarding MTHFR, supplements, and other health concerns. Our team of qualified health professionals respond to these personally. We also address the most common questions on our Customer Support page. It’s all part of our commitment to going the extra mile for our valuable clientele.
The takeaway
Methyl-Life® is proud to be wholly transparent about its manufacturing procedures. Our long list of credentials and certifications reflects our tireless commitment to creating safe and effective products. We seek to not only meet but exceed our customers’ expectations in every way.
Our robust quality assurance practices play a crucial role in upholding the integrity of the US supplement industry and empowering consumers to make informed choices about their health and well-being.
Reference
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416287/
Updated On: July 29, 2023
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Histamine is a type of biogenic tissue amine – L-histidine decarboxylase (HDC) and the cofactor pyridoxal 5’-phosphate or the active form of vitamin B6 mediate the conversion of histidine into histamine (its chemical reaction is represented in figure 1). The key enzymes such as diamine oxidase (DAO) and histamine N-methyltransferase (HNMT) degrade histamine into different by-products.
Figure1. Biosynthesis of Histamine from L-histidine.
As perthe International Union of Pure and Applied Chemistry (IUPAC)nomenclature, the chemical name of histamine is 2-(1H-imidazol-4-yl)ethanamine.
Essentially, the biogenic amines such as histamine, tyramine, putrescine and cadaverine at low concentrations have been reported to possess hazardous adverse effects on the human body. The storage of histamine is principally in lymph nodes, basophils, mast cells, gastric enterochromaffin cells and thymus. There are four histamine receptors, namely, H1, H2, H3 and H4, distributed in various parts of the human body. Histamine binds with respective receptors and displays the pharmacological effects.
Histamine exhibits many biological processes,
Enzymes such as diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT) are actively involved in the metabolism of histamine by negating high levels of histamine in the human body.
Other names of DAO are histaminase and amiloride-binding protein that facilitates the oxidative deamination of histamine. The critical role of DAO is to eliminate the excess histamine and regulate the levels of histamine entering the blood circulation from the digestive tract. The expression of DAO is found in a few specific tissues such as the placenta, kidney, small intestine and ascending colon.
The primary function of HNMT controls histamine expression and its biosynthesis by N-methylation of histamine in various organs including kidney, liver, colon, spleen, spinal cord cells, ovaries, bronchi and trachea.HNMT selectively metabolizes histamine in the central nervous system. DAO can metabolize not only histamine, but it also metabolizesother biogenic amines like cadaverine and putrescine.
Also Read: Can Folic Acid Affect Your Child’s Appetite?
Histamine unveils its pharmacological effects through binding to various histamine receptors (H1, H2, H3 and H4), thereby initiating appropriate pharmacological activities.
Table 1. Effects of various concentrations of histamine.
Histamine concentration in plasma (ng/mL) | Pharmacological and clinical effects |
---|---|
0-1 | Optimal concentration – no histamine intoxication and poisoning |
1-2 | Escalation in heart rate and gastric acid secretion |
3-5 | Tachycardia, headache, pruritus, urticaria and flush |
6-8 | Reduction in arterial pressure |
7-12 | Bronchospasm |
~ 100 | Cardiac arrest |
Histamine intolerance or enteral histaminosis is an imbalance between the histamine degradation system and metabolism of ingested histamine. Basically you’ve eaten more histamine-producing things than your body can get rid of, so you’re dealing with an imbalance. Histamine intolerance is also known as a medical condition that occurs due to reduced diamine oxidase (DAO) activity, which leads to the accumulation of histamine in plasma and creates damaging effects.
Histamine intolerance affects at least 1 percent of the global population. It’s interesting to note that, of those, around 80% are middle-aged women.
With an abundant presence of histamine receptors throughout the human body, histamine intolerance presents most of the clinical manifestationsin various organs such as cardiovascular (tachycardia, palpitations and collapse), gastrointestinal tract (abdominal pain, constipation, diarrhea, emesis, bloating, distention, flatulence, nausea, diarrhea and postprandial fullness), nervous system (dizziness and headache), respiratory system (dyspnea, nasal congestion, rhinorrhea and rhinitis) and skin (eczema, flush, inflammation, pruritus and urticaria).
Also Read: What Does Methylfolate Do For Your Body?
Histamine intolerance is of two different types,
Primary Histamine Intolerance
Secondary Histamine Intolerance
Single nucleotide polymorphisms (SNPs) in any gene often create an inactive state of a particular protein. The genes encoding enzymes L-histidine decarboxylase, diamine oxidase and histamine N-methyltransferase have been extensively studied for their SNPs. These SNPs result in the formation of aprotein with altered activity, followed by histamine build up and therefore produce the symptoms of histamine intolerance.
Vegetables | Eggplant, pumpkin, sauerkraut, spinach, tomato, avocado, olives, pickled and canned vegetables. |
Fruits | Citrus fruits, banana, pineapple, cherry, cranberry, currant, date, loganberry, nectarine, orange, grapefruit, prunes, plums, raisins, raspberries, strawberries, fruit dishes, jams and fruit juices made with high histamine content ingredients. |
Meat, poultry and fish | All fish (if they are not freshly caught), shellfish, refrigerated meats, processed, smoked and cured meats. |
Eggs | Raw egg whites, eggnog, hollandaise sauce and milk shakes. |
Fats and oils | All fats and oils with preservatives and colorants, prepared gravy, commercially available salad dressings and hydrolyzed lecithin |
Spices and herbs | Anise, nutmeg, cinnamon, cloves, curry powder, paprika and foods with spices labelling. |
Nuts and seeds | Walnuts and cashews |
Legumes | Soy, lentils, beans and peanuts |
Bread and cereals | Dry dessert mixes, baking mixes, foods cooked in oils consisting of butylated hydroxy anisole, butylated hydroxy toluene and hydrolyzed lecithin |
Milk and dairy | All cheese, buttermilk and yogurt (except particularly cultured with a low histamine probiotics) |
Sweeteners | All artificial sweeteners, processed sugars, candies, confectionery, cake decorative consumables, flavoured syrups, prepared dessert fillings, icings and frostings and spreads with histamine-rich ingredients. |
Beverages | Coffee, carbonated soda and drinks, alcohol when in large amounts, all tea and drinks with flavour or spices. |
Miscellaneous food items | Chocolate, cocoa, carob, products with artificial flavours, colorants and preservatives, flavoured gelatin, crustaceans, mincemeat, prepared relishes and olives, soy sauce, canned foods, ready meals, pickled and fermented foods, vinegar, yeast and its extracts, wheat germ, benzoates, sulphites, nitrites, glutamates, food dyes and commercial ketchup. |
Histamine isa tissue amine and chemical molecule that gets biosynthesized by the decarboxylation of the amino acid, histidine. The biosynthesis of histamine is catalyzed by the presence of L-histidine decarboxylase and the co-factor pyridoxal 5’-phosphate or the active form of B6 (the chemical reaction is presented in figure 1 below). Of all biogenic amines observed in foods, the excessive levels of histamine and tyramine are considered highly toxic and produce unwantedeffects in the human body.
In 1910,The pioneer researchers in the biogenic amines, Dale and Laidlaw, clarified the physiological and pathophysiological functions of histamine in our bodies. Biosynthesized histamine is stored in basophils, mast cells, gastric enterochromaffin cells, lymph nodes and thymus.
Histamine is involved in several physiological functions such as stimulation of gastric acid secretion and nociceptive nerve fibers, alteration of blood pressure, inflammation, increased vascular permeability, cytokine production, smooth muscle contraction and vasodilatation. Histamine is also synthesized in the brain, specifically in the neurons present in the posterior region of the hypothalamus.As a neurotransmitter, it maintains wakefulnessand carries impulses like pain and itching sensations. Of all G-protein-coupled receptors, H1, H2, H3 and H4 interact with histamine and activate the signal transduction pathways, thereby initiating the biological mechanisms.
Also, histamine actively participates in local immune response, immunomodulation, hematopoiesis, day-night rhythm, wound healing effects and regulation of histamine- and polyamine-induced cell proliferation and angiogenesis in various tumor models and intestinal blood supply. As per the concentration of histamine present in the plasma, different activities are exhibited as mentioned in the below table 1 (Adapted from Mainz et al., Am. J. Clin. Nutr. 2007).
There are two important pathways in the histamine metabolism, namely diamine oxidase (DAO)-dependent and histamine N-methyl transferase (HNMT)-mediated metabolic pathways. DAO facilitates the oxidative deamination of the primary amine group of histamine. Conversely, in the second pathway, the enzyme HNMT converts histamine into 1-methylhistamine through methylation of the secondary amine “N” ofthe imidazole heterocyclic ring.
In a nutshell, based on the need for physiological processes in the human body, the deamination and methylation reactions are catalyzed by the enzymes, DAO and HNMT respectively. DAO converts histamine into imidazole 2-acetaldehyde, followed by imidazole acetic acid and finally, imidazole acetic acid riboside is formed. Conversely, Histamine is metabolized in the presence of HNMT to obtain methylimidazole acetic acid through the production of intermediate methylimidazole acetaldehyde.It is worth noting that the conversion of histamine into different by-products is the protective role of DAO and HNMT against excess histamine, either from ingested foods or produced by the intestinal microbiota. Therefore, both enzymes DAO and HNMThelp balance and maintain optimum levels of histaminein the human body.
The deficiency and single-nucleotide polymorphisms (SNPs) of enzymes including L-histidine decarboxylase, DAO and HNMT may be suggested an influential role in histamine intolerance. Research studies have revealed that more than 50 SNPs in the DAO-encoding gene have been detected to date. Some of key SNPs (namely rs10156191, rs1049742, rs2268999 and rs1049793) discovered in Caucasian people could produce a protein with impaired activity. Individuals of Asian and African decent may be more affected by SNPs rs45558339 and rs35070995 which have also been reported to show DAO enzyme deficiency. On the another hand, the main SNP related to HNMT (rs11558538) has been associated with reduced HNMT activity. Overall, these SNPs lead to reduced or deficient enzyme activity, which increases the levels of histamine in the plasma and is then typically followed by a histamine intolerance reaction (particularly in these individuals with DAO and HNMT SNPs – or genetic mutations).
Also Read: How does histamine affect anxiety?
Histamine and other biogenic amines such as tyramine, putrescine and cadaverineare present in varying concentrations in different foods, which increases as theyage. The following determines the formation of biogenic amines in food:
IEither food that we consume or proteolysis reactions during food processing and storage may yield free amino acids.Plenty of bacterias and a few yeast types demonstrate high L-histidine decarboxylase activity (assisting the conversion of histidine into histamine) as a result, this increases histamine production. It’s worth noting that high levels of histamine and other biogenic amines are typicallyfound in products of microbial fermentation which include processed meats, aged cheeses, sauerkraut and wine, also in microbially spoiled food. So, the presence of histamine, tyramine, putrescine and cadaverineare allconsidered as indicators of food quality.Other biogenic amines can combine with histamine and cause intolerance or adverse effects. Besides histamine-rich food, several foods such as citrus fruits, a few types of fish and licoriceactually contain less histamine; however, they canstimulate a histamine release from mast cells.The mechanism behind this stimulation of endogenous histamine from these particular foods has not yet been discovered.The concentration of histamine in various food categories is presented in Table 2.
Table 2. Histamine content in various types of food categories (Adapted from Bover-Cid et al., 2014).
Food types | N | Histamine content (mg/kg) | |
---|---|---|---|
Average | Maximum |
Fruits, plant-based products and vegetables |
Cereals | 28 | 0.12 | 0.89 |
Chocolate | 25 | 0.58 | 0.56 |
Fruits | 136 | 0.07 | 2.51 |
Legumes | 11 | ND | ND |
Nuts | 41 | 0.45 | 11.86 |
Spices | 12 | ND | ND |
Vegetables | 98 | 2.82 | 2.51 |
Alcoholic beverages |
Beer | 176 | 1.23 | 21.60 |
Red wine | 260 | 3.81 | 55.00 |
White wine | 83 | 1.24 | 21.60 |
Fish and other meat products |
Canned fish | 96 | 14.42 | 657.05 |
Fresh fish | 136 | 0.79 | 36.55 |
Semi preserved fish | 49 | 3.48 | 34.90 |
Fresh meat | 6 | ND | ND |
Cooked meat | 48 | 0.30 | 4.80 |
Cured meat | 23 | 12.98 | 150.00 |
Dry fermented sausages | 209 | 32.15 | 150.00 |
Dairy Products |
Pasteurized milk cheese | 20 | 18.05 | 162.03 |
Raw milk cheese | 20 | 59.37 | 389.86 |
Unripened cheese | 20 | ND | ND/td> |
Although histamine is involved in a copious number of physiological mechanisms in our bodies, the ingestion of foods containing high levels of histamine causes damaging effects on the body. The balance of histamine is reliant on the body’s histamine degradation systems functioning properly;this is required for the body to appropriatelyregulate theexcess levels of histamine.
Histamine intoxication is also a type of food poisoning thatcan happes after the consumption of foods with high histamine levels (higher than 500 mg/kg) which actually subjugates the degradation mechanisms.In 2018, a meta-analysis was performed to identify the foods, which typically cause histamine intoxication. The study covers research data between 1959 and 2013 that focus on several studies of histamine intoxication and revealed that the causative food in 98% of the cases accounted for was fish and the remainingcases were due to cheese.
Histamine intoxication is essentially characterized by a short incubation period with low to moderate severity and subsiding in a few hours. The symptoms of histamine intoxication affect the skin, gastrointestinal tract, hemodynamic and neurological functions.
The adverse effects of histamine intoxication are listed below.
Cardiovascular system
Gastrointestinal tract
Nervous system
Respiratory system
Skin
Table 3. Three-step dietary adjustment (Adapted from Imke Reese et al., 2017).
Phase | Aim | Recommendation | Duration |
---|---|---|---|
I: Avoidance | Reduce symptoms to a great extent | A mixed diet emphasizing vegetables and reduced biogenic amine intake (specifically histamine)Nutrient optimizationChange in meal compositionBalanced diet | 10-14 days |
II: Test | Expansion of food choice under consideration of individual risk factors (stress, medication, menstruation, etc.) | Targeted re-introduction of suspected foodsDetermining individual histamine tolerance | Up to 6 weeks |
III. Long term diet | A balanced supply of nutrientsGood quality of life | Individual nutritional recommendations |
The COVID-19 pandemic has caught the whole world by surprise. Suddenly our lives took a 180 degree turn. We are learning to get used to what people call “the new normal”. We have been dealing with the fear, new rules, and social isolation.
Scientists from all over the world are facing this same scenario of total uncertainty, trying to fight what seems to have become the world´s most publicized enemy.
The problem is that everything´s still very recent and although we have made great progress since the discovery of the virus, there are still a lot of things that we don´t know.
COVID-19 seems to affect all groups, however higher mortality rates are observed amongst the elderly, and people with comorbidities such as hypertension, diabetes, cancer, and cardiovascular diseases(1).
Some authors believe that obesity should be considered a risk factor since it was previously associated with increased mortality in patients with H1N1.
This is because obesity is associated with decreased respiratory capacity and lung function.
Moreover, the increased inflammatory cytokines associated with obesity may contribute to the increased morbidity in obese COVID‐19 patients(2).
That is one reason why researchers are investigating the role of nutrition on COVID-19 susceptibility and long-term consequences.
Obesity can be associated with the Western diet which tends to be high in saturated fats, refined carbohydrates and sugars, but low in fiber, unsaturated fats, and antioxidants.
Consuming high amounts of saturated fatty acids can impact the immune system’s response, making it harder for the body to fight and kill viruses.
Besides the fact that consuming saturated fats leads to an inflammatory state, including in the lungs, which could contribute to COVID-19 pathology(2).
That´s why at times like this we need to look more closely at our food habits, especially the nutrients we eat. Several nutrients help in the functioning of our immune system.
As an example, we have vitamins A, B6, B12, C, D, E, and folate(3).
The B-Complex vitamins play an important role in our body. They help to maintain the health of the red blood cells, aid in the functioning of the nervous system and participate in the synthesis of our genetic material(3).
For example, deficiency in B12 can lead to anemia, neurological problems, and even cardiovascular diseases. The latter is due to B12 involvement in homocysteine metabolism(3).
Vitamin B12 can be obtained from food, the sources are fish, meat, poultry, eggs, milk, fortified cereals, and B12 supplements.
However, not everyone consumes the recommended daily amount they need. Moreover, some people can´t absorb nutrients properly, or simply have a higher requirement of this nutrient, such as elderly people, kids, those with genetic mutations, and pregnant woman(3).
Folic acid (the synthetic form of folate, or vitamin B9) can be found in leafy green vegetables, fruits, dried beans, peas, and nuts, enriched bread, cereals, and other grain products.
Vitamin B6 sources are animal protein, breads, wholegrain cereals, milk, vegetables, and fortified foods. These two vitamins also participate in the metabolism of homocysteine(3).
Homocysteine (Hcy) is a type of amino acid, the building blocks that are used to build proteins. Homocysteine is produced by a process called demethylation (removal of a methyl group (CH3) from a molecule) of the amino acid methionine.
Methionine is one of the 11 essential amino acids which means our body can´t produce it and we have to get it from our diet, especially from animal protein sources(4).
When a methyl group is added to a methionine molecule, we have the production of homocysteine. For this reaction to occur, we need the help of another type of protein, an enzyme named methionine synthase(4).
Three other components also have an important role in this process: vitamins B6, B12, and folate. In general, when the levels of those vitamins are low, we have an increase in Hcy levels.
Deficiencies in these vitamins, together with genetic factors affecting enzymes involved in Homocysteine metabolism can lead to an increase in Homocysteine levels in the blood. When this happens, the blood vessels become irritated, and the consequences are abnormal clotting and increased risk of cardiovascular diseases.
Hyperhomocysteinemia (high levels of Hcy in the blood) is linked to atherosclerosis (hardening of the arteries) which can lead to a heart attack or stroke, and also to arterial thrombosis and venous thromboembolism.
Other health problems that have been associated with hyperhomocysteinemia are osteoporosis, dementia, and Alzheimer's.
A doctor may request a homocysteine test when she/he suspects a vitamin B12 or folate deficiency, when the patient has a family history of cardiovascular diseases(4) or even when the patient has a known MTHFR genetic variant.
Homocysteine levels can increase with age, overuse of tobacco, and the use of certain medications. People with hyperhomocysteinemia may benefit from the supplementation of folate and vitamin B12(4).
One of the main challenges in the context of the new coronavirus disease is to find biomarkers that will help healthcare professionals better identify patients with an elevated risk of progression(5).
People who suffer from cardiovascular diseases are more likely to develop severe symptoms of COVID-19. These patients have higher a chance of needing intensive care treatment and even dying from the disease.
This is because the virus can cause damage to the cardiovascular system resulting in injuries to the heart muscle, arrhythmias, myocarditis, and shock(6).
It is well-known that elevated levels of homocysteine in the blood increase the incidence of damage to the vessels. High levels of homocysteine can also stimulate atherosclerosis and increase the risk of thrombosis(7).
Some authors believe that homocysteine levels should be measured in patients with COVID-19 to assess the risk of cardiac and pulmonary complications.
They support the idea that it is a simple test that could be made at the time of hospitalization or diagnosis(5).
One study carried out with 273 COVID-19 patients aimed to investigate the potential parameters associated with imaging progression on chest computed tomography (CT).
This exam uses x-ray equipment to search for abnormalities and to help in the diagnosis of cough, shortness of breath, chest pain, fever, and other chest symptoms(5).
Currently, the PCR (polymerase chain reaction) is the gold standard in the diagnosis of the new coronavirus, and the CT is used to help in this diagnosis.
The most common findings in the CT exam of COVID-19 patients are pulmonary ground-glass opacities (a pattern that is observed when the lungs are sick), vascular thickness, and consolidation (when the air that normally fills the airways in the lungs is replaced with fluid)(8).
In some cases, both lungs are affected and CT can be used to assess the severity of the lung involvement in COVID-19. The alterations can progress very quickly, with CT exam showing an enlarged and increased extent of ground-glass opacity and consolidation(8).
The researchers investigated which factors could help predict this chest CT progression in patients with COVID-19 in an attempt to find proper biomarkers(5).
They observed that chest CT progression occurred one week after admission to the hospital. The majority of these patients were older when compared to those who didn´t progress(5).
In patients that had their blood tested for homocysteine levels, it was observed that those levels were higher in patients who had progressed imaging(5).
This is an important finding because chest CT progression is indicative of more severe disease. Learning how to identify the patients at risk of progression will help healthcare professionals to take quick actions and provide better treatment for these patients(5).
So essentially this gives us an important clue – high homocysteine may be an indicator of those who could have a harder time fighting COVID-19 if it’s contracted.
As we discussed earlier and in other articles, elevated levels of homocysteine can be toxic for our bodies. The role of homocysteine in coronavirus is not yet well understood.
However, there´s evidence that high homocysteine levels are associated with other infectious diseases caused by viruses such as HIV, hepatitis, and HPV(9).
Thus, hyperhomocysteinemia might be one of the mechanisms involved in the progression of the disease.
Since increased levels of homocysteine in the bloodstream can be associated with a worse prognosis of COVID-19, taking measures to reduce your homocysteine levels is likely a good idea.
One of the possibilities is to change your diet. If you have a vitamin deficiency, you can increase your vitamin B12 and folate intake.
This can be done by simply adding vitamin B-rich food to your meals, things such as green vegetables, orange juice, and beans.
Some people may have more difficulty obtaining an adequate amount of these vitamins through diet alone. Unfortunately, not everyone can solve these challenges with a healthy diet, especially older people who suffer from malnutrition for a variety of reasons such as tiredness, the difficulty of access (fixed incomes), and poorer digestion.
We know that older people are amongst the group with a higher risk of developing severe symptoms of COVID-19. That´s why it may be helpful to take vitamin B supplements – specifically folate, B12 and B6.
When you eat food containing vitamin B9 or food enriched with synthetic folic acid, the folate present in fortified foods, a perfect body should metabolize it into L-methylfolate for cellular absorption and health benefit.
However, over half of the population has a common mutation in the specific genetic pathway that is responsible for this conversion, it’s referred to as MTHFR.
And the characteristics of this mutation are not only low folate absorption, but also high homocysteine levels. It is understood that when you consume L-methylfolate in its direct form, you´re already getting the most “usable” and “active” form of vitamin B9 that your body can immediately absorb AND use to normalize those otherwise high homocysteine levels.
That means your body won´t have to take additional steps to metabolize the folate and the folate will start balancing those homocysteine levels for optimal health.
One important study showed that a three-month intake of a dietary supplement containing methylfolate can significantly reduce blood homocysteine levels in patients with diabetes, which can also help to prevent the occurrence of cardiovascular complications(10).
So taking L-Methylfolate directly improves your cardiovascular health in addition to boosting your immune system and both of these seem to be key indicators in helping you prevent and fight COVID-19.
Taking care of our health, especially the nutrients we provide to our body has never been more important. The right nutrients, when ingested in adequate amounts, can make our immune system better prepared to deal with invaders.
Thus, we become sick less frequently and recover faster from illnesses.
SARS-COV2, the virus that causes the new coronavirus (COVID-19), is not yet fully understood. Researchers are working hard on a global initiative to try to understand how the virus behaves so that we know how to fight it.
Taking into account the role of nutrition and food in our body’s defense against viruses and other invaders is hugely important.
Similarly we may find the lack of proper nutrition also playing a role in the development and progression of COVID-19.
B Vitamins are nutrients that play an important role in immune defense. Also, it’s very important to note that when vitamin B12 and folate levels are below normal, homocysteine blood serum levels increase, which is NOT good.
Elevated homocysteine can lead to cardiovascular complications, which is one of the symptoms of severe COVID-19. Hyperhomocysteinemia may be associated with the worsening of the coronavirus disease and can serve as a biomarker of disease progression.
Supplementation of an active form of vitamin B12 and L-Methylfolate could help reduce the risk of cardiovascular complications in patients with COVID-19 especially in older people who usually suffer from malnutrition, and are at higher risk of developing severe symptoms of the disease. More research is needed to reach a conclusion.
In the meantime, consider Methyl-Life’s™ B-Methylated II product which is made up of the specialized active form of folate, L-Methylfolate (3 mg), PLUS the active B12 form, methylcobalamin (3.75 mg).
This professional strength formula provides dosage level amounts designed specifically to help reduce your body’s homocysteine levels and increase your cardiovascular health.
It comes in a convenient chewable that is best dissolved sublingually (under the tongue) for optimal absorption (B12 is well-known to be best absorbed under the tongue and not through the stomach). What an affordable way to give yourself some extra COVID-19 nutritional assurance!
Methyl-Life™ knows methylation better than most anyone, we’ve been working with doctors and selling these nutrients since 2011, long before coronavirus ever became a concern. We are experts on L-Methylfolate and how it affects homocysteine levels.
AND we sell the very purest L-Methylfolate on the planet, and we’re not just saying that, we can prove it to you. A recent study has revealed that our proprietary form of methylfolate is three times purer than any other L-Methylfolate competing in the market today, including the pharmaceutical version.
Don’t kid yourself, not all nutritional supplements are the same – not even the ones who make claims that they are. Go with a sure thing when it comes to your health and COVID-19 protection.
Our production runs get third-party tested to verify that what the label says ACTUALLY IS IN YOUR BOTTLE.
As with taking any supplement, it is strongly advised that you consult with a qualified healthcare practitioner before beginning any treatment.
Methyl-Life™ provides free Methylation Protocols for download, so you can decide what’s best to take for your specific methylation needs.
1. Butler MJ, Barrientos RM. The impact of nutrition on COVID-19 susceptibility and long-term consequences. Brain , Behavior , and Immunity. 2020;(January).
2. Dietz W, Santos-burgoa C. Obesity Obesity and its Implications for COVID-19 Mortality. 2020;28(6):22818.
3. Calder PC, Carr AC, Gombart AF. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. :1–10.
4. Giovanni Ponti, Cristel Ruini AT. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company ’ s public news and information. Med Hypotheses J. 2020;143(January).
5. Yang Z, Shi J, He Z, Lü Y, Xu Q, Ye C, et al. Predictors for imaging progression on chest CT from coronavirus disease 2019 ( COVID-19 ) patients. 2020;12(7):6037–48.
6. Bispo I, Costa S, Bittar CS, Rizk SI, Everaldo A, Filho DA, et al. Review Article The Heart and COVID-19 : What Cardiologists Need to Know. 2020;805–16.
7. Ferreira JGP, Bittencourt JC, Adamantidis A. Melanin-concentrating hormone and sleep. Curr Opin Neurobiol [Internet]. 2017;44:152–8. Available from: http://dx.doi.org/10.1016/j.conb.2017.04.008
8. Chate RC, Kaiser E, Nunes U, Bastos R, Passos D, Borges G, et al. Presentation of pulmonary infection on CT in COVID-19 : initial experience in Brazil. 2020;46(2):4–7.
9. Abike F, Engin AB, Lutfi O, Canan T, Kutluay L. Human papilloma virus persistence and neopterin , folate and homocysteine levels in cervical dysplasias. 2011;209–14.
10. Schmidl D, Howorka K, Szegedi S, Stjepanek K, Puchner S, Bata A, et al. A pilot study to assess the effect of a three-month vitamin supplementation containing L-methylfolate on systemic homocysteine plasma concentrations and retinal blood flow in patients with diabetes. 2020;(September 2019):326–33.
Finding out that you have a histamine intolerance may come as a surprise. Some people may find it a huge relief. Finally, an explanation for their itchy eyes and runny nose!
Others will bemoan their bad luck, and wonder what the heck to do about it.
In any case, the protocol is the same: switching to a low histamine diet. But what is that exactly? What foods are low in histamine and what foods are not? What even IS histamine?
We’ll explain all that - and more.
Histamine is a chemical that occurs naturally in some foods and is also produced by your body.
It’s actually known as an autacoid, which means it acts like a local hormone near where it is synthesized in the body. The highest concentrations of histamine are found in your intestinal mucosa, skin, and bronchial tissues.80
Although an inflammatory reaction can be quite unpleasant, histamine is very important in protecting your body from potential harm. It acts like an armed guard, sounding the alarm to let your body know that something foreign has entered and that it needs to be fought off.
This causes your immune system to respond with inflammatory chemicals that help get rid of the invader - known as an allergen - that’s bothering you.
When produced during a local immune response, histamine’s main role is to cause inflammation. Its release causes your capillaries to become more permeable to white blood cells and other proteins, which allows the white blood cells to target and attack foreign bodies in the affected tissue.
As one of the most versatile molecules in your body, histamine can cause a huge range of effects depending on where it’s released.
Immune Cell Release
Histamine is produced as part of your immune system’s response in order to trigger inflammation. Basophils and mast cells secrete histamine when your body detects one of these invaders. These cells reside in connective tissue and act as potent effector cells of the innate immune system.
Mast cells are the major producer of histamine and express many receptors on their surface. These receptors are activated through stimulants such as allergens, complement peptides, and neuropeptides, which cause the mast cells to release various inflammatory mediators including histamine.
When released, histamine causes smooth muscle contraction in the intestines (often causing cramps and diarrhea), expansion of blood vessels (often causing low blood pressure), mucus secretion in the nasal passages and GI tract, and many other physiologic effects that are intended to fight off invaders.
When the ‘threat’ is passed, histamine levels return to normal, and symptoms subside.
Stomach Cell Release
Histamine is also released from enterochromaffin-like cells in the stomach, triggering acid secretion from parietal cells. This increases acidity in the stomach to kill off any dangerous invaders.
Brain Cell Release
Histamine is also produced in the hypothalamus. It acts as an excitatory neurotransmitter and is involved in regulating the sleep-wake cycle.
Histamine is a byproduct of the amino acid histidine. It’s created when certain strains of bacteria or yeasts convert histidine into histamine.
Histidine is present in most protein-rich foods such as meat, fish, eggs, soy, whole grains, beans, and nuts. Although most protein-containing foods can form histamine under the right conditions, the foods containing the highest amounts are aged and fermented foods. Fresh foods contain very little or zero.
Histamine intolerance occurs when your body can’t cope with the levels of histamine that have accumulated. This build-up can lead to symptoms that are very similar to an allergic reaction.
It’s estimated that around 1% of the population has histamine intolerance; most of whom are middle-aged women. Research suggests that estrogen may be to blame here, because it activates histamine release from mast cells, while progesterone inhibits it.
Because histamine plays so many different parts in how your body functions, symptoms of an intolerance are broad and can easily be confused for other things, such as food allergies.
Some of the most common symptoms of histamine intolerance to be aware of include:
Digestive issues
Abdominal cramping, bloating, diarrhea, and other gastrointestinal discomforts. Histamine plays a part in breaking down food. If your body isn’t able to do this properly, you’ll end up with symptoms like gas, bloating, diarrhea, and stomach pain.
Headaches and dizziness
Histamine can cause the blood vessels in your brain to dilate, which can lead to headaches and lightheadedness.
Respiratory issues
Nasal congestion, sneezing, and other respiratory problems. Again, dilated blood vessels in the nasal passageways tend to cause sneezing and congestion. Histamine can also affect other parts of your respiratory system beyond your nose, including your airways. In extreme cases of histamine intolerance, you may have trouble breathing.
Dermatological problems
Rashes, eczema, and itchy skin are also a result of inflammatory reactions in the skin.
Cardiovascular reactions
A racing heart or palpitations is caused by histamine acting directly on cells in your heart.
There are a large number of bacteria that live in our bodies, primarily in our guts. In fact, we have around ten times more bacteria than we do cells. While most people believe bacteria to be negative -- and they can be in many instances -- some bacteria will do a lot of good for our bodies.
Probiotics are one such classification of these “good types” of bacteria. They’re living microorganisms that can be ingested by mouth to provide a wide range of benefits. Probiotics shouldn’t be confused with prebiotics, which are dietary fibers that act as food for the probiotics.
Having too much bad bacteria in your gut can cause an imbalance and be linked to various health diseases, but taking probiotics can help normalize the balance of good and bad bacteria in the intestines. This will help your gut flora to get back to functioning properly.
If you’ve been instructed by your doctor to take a probiotic, there are several things you should know so you can better prepare yourself. We’ll break it all down for you below. First of all, not all probiotics are equal - in fact, most species of probiotics cannot survive the stomach acids which means 90% often die before reaching the intestine where they’re supposed to flourish and do their jobs to populate and beat out the bad bacteria. If you want to ensure your probiotic will, in fact, reach its destination intact (the intestines), then consider a spore-based probiotic. The way you’ll know it’s a spore-based probiotic is that the specific names of the strains will start with the word ‘Bacillus’. What’s unique about a spore-based probiotic is that it can live and survive in multiple environments (especially harsh ones). When it feels threatened by the environment, say stomach acid or an antibiotic, a Bacillus strain can turn itself into a ‘spore’ which is like a turtle going into an airtight shell that very little can penetrate, then when the environment around it becomes ‘safe’ again, it will turn back into the live bacteria it needs to be in order to do its health-giving jobs in the gut.
Probiotics will do a lot of positive things, but many people might experience some minor side effects, especially in the first weeks. This is largely due to our bodies not being used to the change, but you should know that this is common and temporary.
Some of the side effects might include increased levels of gas, abdominal pains, loose stool, or bloating. The reason taking a probiotic can be so challenging in the beginning is because you’re trying to repopulate your gut with good bacteria. And in essence, you’re kind of bringing in a good army to get rid of the bad guys, and when the good guys are killing off the bad guys, you’re often getting some of these ‘die-off’ symptoms. This is merely your body getting rid of the dead bad guys (which is exactly what you want it to do).
But if the die-off symptoms you’re experiencing start to become difficult to bear, you can always try taking half of a dose, taking it every other day or maybe even both to ease the symptoms. Everyone will be able to tolerate probiotics at different levels (often because we all have different levels of die-off that we’ll experience). Listen to your body and go at a rate and speed that feels doable. The old adage, ‘no pain, no gain’ is an outdated misnomer and is not the way we should be treating our bodies. The same goes for the idea of ‘if a little is good, then a lot must be better’, try to take probiotics in moderation so that the journey is not miserable for you. And realize that if someone takes a full dose of the probiotic easily within a week but it takes you 8 weeks to get to a ‘full dose’, that’s totally okay. It’s not a race and your body will thank you for not making it one.
After the first few weeks, the probiotics will typically start to settle in and do what they do best. During the first couple of months is when you’ll start to notice some of the positive effects that you may have been missing out on for the majority of your life.
You will notice a much smoother digestion process and more normalized bowel movements. The abdominal pain, bloating, and excessive gas will start to go away and you’ll see an improvement in your immune system. By the fourth week, a majority of the antibodies in your system will be flushed out and able to reset.
This first month is all about getting used to what will become your new norm. And you may be surprised by how much the bacteria in your gut contributes to the way you feel on a daily basis.
With the Coronavirus lockdown still active, there are a variety of supplements being talked about right now due to their benefits to the immune system. As we know, the immune system is our body’s personal defense against viruses and bacteria. A strong immune system will help keep you healthy during difficult times.
Of all the vitamins and minerals being discussed, there’s one that isn’t getting enough attention -- Selenium. Not only is it found in a variety of different supplements already, but it has been estimated that nearly one billion people in the world suffer from a selenium deficiency.
Selenium is an essential mineral that your body can’t produce on its own. This means you must consume it in your diet on a daily basis. According to the National Health Institute, you should be receiving 50-60mcg per day.
We will frequently find selenium in various foods we eat, such as brazil nuts, fish, ham, pork, beef, eggs, brown rice, and baked beans. How much selenium is in each food will depend on the amount of selenium in the soil it grew in.
If you’re receiving dialysis, are living with HIV, or have Crohn’s disease, there’s a good chance your body isn’t properly absorbing the selenium in your diet. In this case, supplementing would be an easy way to solve that.
As we mentioned earlier, the immune system helps our body fight infections, diseases, bacteria, and pathogens. Without it, you would be highly vulnerable to any viruses roaming around. Much like every other system in our body, certain nutrients will act as fuel for the immune system -- including Selenium.
Selenium is known for its antioxidant properties, which means it helps reduce oxidative stress in the body. With a healthy balance of free radicals and antioxidants in the body, your immune response will receive a boost and inflammation will be reduced. Together, this will lead to a stronger immune system.
Also Read: Enzymes: Kind of a Big Deal
That’s not all Selenium has to offer, though. It has been shown to reduce the risk of certain cancers by limiting DNA damage, as well as protecting your body against heart disease.
Although there are no cures for the Coronavirus at this time, a healthy immune system can help you reduce your risk of contracting the virus. As always, you should be practicing social distancing and washing your hands frequently.
If you’re looking to add a multivitamin to your daily diet, we have two great ones to choose from. Our multivitamins contain plenty of Selenium -- along with other immune-boosting ingredients.
Contact us today to learn more about our supplements and how they can help you during these difficult times!
As the quarantine lockdown continues, people across the world are still looking for ways to increase their body’s protection against coronavirus. While nothing has proven to be more effective than social distancing and proper hygiene, stepping up your body’s personal line of defense can definitely help.
The immune system is a complex, yet an extremely interesting network of cells, organs, and proteins. Together, they help protect the body from infections, viruses, and diseases. The stronger your immune system is, the harder it will be for those pesky bacteria and pathogens to attack you.
In fact, your immune system will keep a record of every pathogen it defeats -- almost like a journal. This allows them to quickly defeat that bacteria if it were to show up again. This is why vaccines will carry the pathogen, allowing your immune system to identify it as an attacker.
A nutrient-rich diet, regular exercise, quality sleep patterns, and avoiding drugs or alcohol are excellent ways of boosting your immune system. Unfortunately, many people will find it difficult to make the necessary lifestyle changes.
If getting enough nutrients is a struggle for you, supplements can help you reach your daily recommended amounts -- though they shouldn’t be used as meal replacers. When looking for more protection against coronavirus, there are three supplements that we recommend you consider adding to your daily routine -- Vitamin D, Vitamin B12, and Zinc.
Vitamin D is a fat-soluble nutrient that many people are already deficient in. You can find it fortified in some foods and naturally in mushrooms, fatty fish, and egg yolks. Believe it or not, our body will produce Vitamin D on its own when our skin is exposed to sunlight -- and this is generally our most abundant source of this nutrient.
Unfortunately, the quarantine has resulted in many people neglecting sunlight exposure and instead electing to stay inside. For a nutrient we are already deficient in, a majority of people are now getting even less.
Not to mention, Vitamin D plays an essential role in the immune system. It not only makes white blood cells more effective at killing pathogens, but it also has anti-inflammatory properties that increase your body’s immune response.
Vitamin B12, also known as cobalamin, is a water-soluble vitamin that plays an essential role in the immune system. Because it is water-soluble, our body will excrete any excess Vitamin B12 we consume, making it essential that we consume it every day.
Zinc is known as the Mighty Mineral and for a good reason. It comes with a wide range of benefits and roles in the body, one of which includes the immune system. It will help improve inflammatory response, while also aiding immune cell development and communication between cells.
With Zinc, Vitamin B12, and Vitamin D, you can start to give your immune system the boost it needs during these difficult times. At Methyl-Life, we offer a multivitamin that contains a healthy dose of all three -- as well as other essential vitamins and minerals.
Contact us today to learn more about our supplements and how they can help you shape a better future yourself -- even with the world currently on hold.
Visit Methyl-Life® Covid-19 blog for more posts.
Canrong WU,a,1Yueying YANG,b,1Yang LIU,bPeng ZHANG,bYaliWANG,bQiqi WANG, b Yang XU,bMingxue LI,bMengzhu ZHENG,a,* Lixia CHEN,b,* &Hua LIa,b,*
aHubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
bWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China
A novel coronavirus (SARS-CoV-2) infectious disease has broken out in Wuhan, Hubei Province since December 2019, and spread rapidly from Wuhan to other areas, which has been listed as an international concerning public health emergency. We compared the Spike proteins from four sources, SARS-CoV-2, SARS-CoV, MERS-CoV and Bat-CoVRaTG13, and found that the SARS-CoV-2 virus sequence had redundant PRRA sequences. Through a series of analyses, we propose the reason why SARS-CoV-2is more infectious than other coronaviruses. And through structure-based virtual ligand screening, we foundpotentialfurin inhibitors, which might be used in the treatment of new coronary pneumonia.
Keywords: SARS-CoV-2;Spike proteins;Furin;Inhibitors;Virtual screening
In December 2019, a series of acute respiratory diseases occurred in Wuhan, Hubei Province, China and then spread rapidly from Wuhan to other areas. As of February 17, 2020, a total of 71,444 patients have been diagnosed and 1,775 have died worldwide. This is caused by a novel coronavirus, which was named as "2019-nCoV" by the World Health Organization, and diseases caused by 2019-nCoV was COVID-19. 2019-nCoV, as a close relative of SARS-CoV, was classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses (ICTV) on February 11, 2020.
Coronaviruses (CoVs) are mainly composed of four structural proteins, including Spike (S), membrane (M), envelope (E) and nucleocapsid (N) [1]. Spike, a trimeric glycoprotein of CoVs, determines diversity of CoVs and host tropism, and mediates CoVs binding to host cells surface-specific receptors and virus-cell membrane fusion [2]. Current research found that SARS-CoV-2 belongs to the beta coronavirus genus, and speculated that it may interact with angiotensin-converting enzyme 2 (ACE2) on the surface of human cells through Spike protein, thereby infecting human respiratory epithelium cell [3]. Letko M and Munster Vthen identified the receptor for SARS-CoV-2 entry into human cells to be ACE2 [4].
Coronavirus Spike protein plays a key role in the early stages of viral infection, with the S1 domain responsible for receptor binding and the S2 domain mediating membrane fusion [5]. The process of SARS-CoV infecting the host involves two indispensable cleaving processes which affect the infectious capacity of SARS-CoV. First, Spike was cleaved into receptor-bound N-terminal S1 subunit and membrane-fusion C-terminal S2 subunit by host proteases at S1/S2 cleavage site (such as type II transmembrane serine protease (TMPRSS2), cathepsins B and L) [6,7]. Second, after CoVs are endocytosed by the host, the lysosomal protease mediates cleavage of S2 subunit (S2’ cleavage site) and releases the hydrophobic fusion peptide to fuse with the host cell membrane [8].
Furin, a kind of proprotein convertases (PCs), is located in the trans-Golgi network (TGN) and activated by acid pH [9]. Furin can cleave precursor proteins with specific motifs to produce mature proteins with biological activity. The first (P1) and fourth (P4) amino acids at the
amino acid, ↓:cleavage site). If the P2 position is basic lysine or arginine, the cleavage efficiency
can be improved by about 10 times [10]. Kibler KV et al. demonstrated that the Spike protein S1/S2 and S2′ cleavage sites of the infectious bronchitis virus (IBVs) Beaudette strain can be recognized by fruin, which is a distinctive feature of IBV-Beaudette with other IBVs and has stronger infection ability [11,12]. Based on the characteristics of furin's recognition substrate sequence, some short peptide inhibitors have been developed, such as Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (Dec-RVKR-CMK) and modified α1-antitrypsin Portland (α1-PDX). However, the non-specific and irreversible inhibitory effects on all members of the PC family limit their application [10, 13]. No small molecule inhibitor of furin with good effect and high specificity has been found so far.
The epidemiological observations showed the infectious capacity of SARS-CoV-2 is stronger than SARS-CoV, so there are likely to be other mechanisms to make the infection of SARS-CoV-2 easier. We suppose the main possibilities as follows, first, SARS-CoV-2 RBD combining with ACE2 may have other conformations; second, the SARS-CoV-2 Spike protein can also bind to other receptors besides ACE2; third, Spike is more easily cleaved by host enzymes and easily fuses with host cell membrane. We compared the Spike proteins from four sources, SARS-CoV-2, SARS-CoV, MERS-CoV and Bat-CoVRaTG13, and found that the SARS-CoV-2 virus sequence had redundant PRRA sequences. Through a series of analyses, this study propose that one of the important reasons for the high infectivity of SARS-CoV-2 is a redundant furin cut site in its Spike protein.And through structure based virtual ligand screening, we proposed possible furin inhibitors, which might be potentially used in the treatment of COVID-19.
2.1 Homology Spike protein blast and sequence alignment.
The Spike protein of(GB:QHR63250.1) was downloaded from NCBI nucleotide database. The protein sequence were aligned with whole database using BLASTp to search for homology viral Spike protein (Alogorithm parameters, Max target sequences: 1000, Expect threshold: 10). Multiple-sequence alignment was conducted in BLASTp online and analysis with DNAMAN and Jalview. The evolutionary history was inferred using the Neighbor-Joining method in MEGA 7 software package. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test wasdetermined by 500 replicates. The Spike protein sequence analyses were conducted in snapgene view.
2.2 Furin cleavage site prediction
The prediction of furin cleavage sites were carried out in ProP 1.0 Server (http://www.cbs.dtu.dk/services/ProP/).
2.3 Compounds database
Approved drug database was from the subset of ZINC database, ZDD (ZINC drug database) containing 2924 compounds [14]. Natural products database was constructed by ourselves, containing 1066 chemicals separated from traditional Chinese herbals in own lab and natural-occurring potential antiviral components and derivatives. Antiviral compounds library contains 78 known antiviral drugs and reported antiviral compounds through literature search.
2.4 Homology modeling and molecular docking
3.1 Bioinformatics analysis reveals furin cut site in Spike protein of SARS-CoV-2
Description |
Accession no. |
CS1 sequence |
Furinscorea |
Identityb |
SARS-CoV-2 |
QHR63250.1 |
NSPRRAR/SV |
0.620 |
100% |
Bat-CoV-RaTG13 |
QHR63300.1 |
QTQTNSR/SV |
0.151 |
97.4% |
Bat-SL-CoV |
AVP78042.1 |
HTASILR/ST |
0.170 |
80.3% |
SARS-CoV |
ABF68955.1 |
QLTPAWR/IY |
0.117 |
76.0% |
Bat-CoV HKU5 |
AGP04941.1 |
PSARLAR/SD |
0.697 |
37.1% |
MERS-CoV |
QBM11737.1 |
LTPRSVR/SV |
0.563 |
35.0% |
Rat-CoV |
AFG25760.1 |
TAHRARR/SV |
0.879 |
36.3% |
MHV |
ABS87264.1 |
TSHRARR/SI |
0.861 |
36.9% |
HCoV-HKU1 |
AGT17758.1 |
SSRRKRR/GI |
0.744 |
36.8% |
Rodent-CoV |
ATP66727.1 |
TARRKRR/AL |
0.795 |
37.3% |
Beta-CoVsp |
AYR18670.1 |
ATRRAKR/DL |
0.753 |
35.9% |
Equine-CoV |
BAS18866.1 |
TARRQRR/SP |
0.815 |
37.1% |
Porcine-CoV |
ARC95227.1 |
TSLRSRR/SL |
0.758 |
36.1% |
Bovine-CoV |
QGW57589.1 |
TKRRSRR/AI |
0.780 |
37.5% |
Canine-CoV |
ABG78748.1 |
TQRRSRR/SI |
0.832 |
37.1% |
Camel-CoV HKU23 |
ALA50080.1 |
IDRRARR/FT |
0.718 |
36.5% |
Rabbit-CoV HKU14 |
AFE48805.1 |
TLQPSRR/AI |
0.629 |
37.7% |
Human-CoV OC43 |
AMK59677.1 |
KTRRSRR/AI |
0.720 |
36.8% |
aScores are predicted by ProP 1.0 Server. Scores above 0.5 mean furin cleavable.
bIdentities compared with SARS-CoV-2 Spike protein. |
|
|
The structure-based virtual ligand screening method was used to screen potential furin protein inhibitors through ICM 3.7.3 modeling software (MolSoft LLC, San Diego, CA) from a ZINC Drug Database (2924 compounds), a small in-house database of natural products (including reported common antiviral components from traditional Chinese medicine) and derivatives (1066 compounds), and an antiviral compounds library contains 78 known antiviral drugs and reported antiviral compounds. Compounds with lower calculated binding energies (being expressed with scores and mfscores) are considered to have higher binding affinities with the target protein.
No. |
Drug Name |
Structure |
Pharmacological functions |
1 |
Aminopterin |
|
Anti-tumor |
2 |
Folic acid |
|
Vitamin B9, necessary material for the growth and reproduction of body cells |
3 |
Sulfoxone |
|
Antibacterial effect |
4 |
Silybin |
|
Hepatoprotective effect |
5 |
Diminazene |
|
Insecticidal effect |
6 |
Fludarabine phosphate |
|
Anti-tumor |
7 |
L-Arginine |
|
Nutritional supplement |
8 |
Hydroxystilbamidine |
|
Antifungal effect |
9 |
Methotrexate |
|
Antineoplastic, antirheumatic effects |
10 |
L-dopa |
|
Treatment of Parkinson's
disease |
11 |
Irinotecan |
|
Anti-tumor |
12 |
Cefoperazone |
|
Antibacterial effect |
13 |
Folinic acid |
|
Folic acid supplement |
14 |
Glycerol 3-phosphate |
|
Intermediate for serine
synthesis |
15 |
Valganciclovir |
|
Antivirus |
16 |
Fosaprepitant |
|
Treatment of nausea and vomiting induced by chemotherapy |
17 |
Lomefloxacin |
|
Antibacterial effect |
18 |
Glutathione |
|
Hepatoprotective effect |
19 |
Famotidine |
|
Treatment of gastrohelcosis |
20 |
Imatinib |
|
Anti-tumor |
21 |
Chenodeoxycholic acid |
|
Dissolving gallstones |
No. |
Drug Name |
Structure |
Pharmacological
functions |
Source |
1 |
(-)-Epigallocatechin gallate |
|
Antioxidation, anti-tumor, treatment of depression |
Camellia sinensis |
2 |
Theaflavin 3,3'-di-O-gallate |
|
Antioxidant effect, anti-tumor, anti-virus |
Camellia sinensis |
3 |
Biorobin |
|
Anti-virus |
Ficusbenjamina |
4 |
14-deoxy-11,12- didehydroandrographiside |
|
Anti-virus, anti-inflammatory effect |
Andrographispanicu lata |
5 |
(1S,2R,4aS,5R,8aS)-1-
formamido-1,4a-dimethyl-6- methylene-5-((E)-2-(2-oxo-2,5- dihydrofuran- 3-yl)ethenyl) decahydronaphthalen-2-yl 5-((R)-1,2-dithiolan-3-yl) pentanoate |
|
Anti-virus, anti-inflammatory effect |
Andrographolide derivatives |
6 |
2β,30β-dihydroxy-3,4-seco-friedelolact one-27-lactone |
|
Anti-virus |
Viola diffusa |
7 |
Phyllaemblicin G7 |
|
Anti-virus |
Phyllanthusemblica |
8 |
Andrographolide |
|
Anti-virus, anti-inflammatory effect |
Andrographispanicu lata |
9 |
14-deoxy-11,12- didehydroandrographolide |
|
Anti-virus, anti-inflammatory effect |
Andrographispanicu lata |
10 |
(1S,2R,4aS,5R,8aS)-1-
formamido-1,4a-dimethyl-6- methylene-5-((E)-2-(2-oxo-2,5- dihydrofuran-3-yl)ethenyl) decahydronaphthalen-2-yl 2-aminoacetate |
|
Anti-virus, anti-inflammatory effect |
Andrographolide derivatives |
11 |
2-[[2-O-(6-deoxy-α-L-mannopyranosyl
)-β-D-xylopyranosyl]oxy]-1,8-dihydro xy-6-methoxy-9H- xanthen-9-one |
|
Anti-virus, anti-inflammatory effect |
Swertiakouitchensis |
12 |
Kouitchenside J |
|
Anti-virus, anti-inflammatory effect |
Swertiakouitchensis |
13 |
Stigmast-5-en-3-ol |
|
Antioxidant effect |
Spatholobussuberect usdunn |
14 |
Kouitchenside F |
|
Anti-virus, anti-inflammatory effect |
Swertiakouitchensis |
No. |
Drug Name |
Structure |
Pharmacological functions |
1 |
Suramin |
|
DNA topoisomerase II inhibitor |
2 |
Indinavir |
|
Human immunodeficiency virus Protease (HIV PR) |
3 |
Boceprevir |
|
Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A) Modulator |
4 |
Tenofoviralafenamide |
|
HIV-1 nucleotide reverse transcriptase inhibitor |
5 |
TenofovirDisoproxil |
|
HIV, HBV nucleotide reverse transcriptase inhibitor |
6 |
Acycloguanosine triphosphate |
|
Thymidine kinase of herpesvirus |
7 |
Telaprevir |
|
Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A) Modulator |
8 |
Dolutegravir |
|
Human immunodeficiency virus Integrase (HIV IN) |
9 |
Maraviroc |
|
1.C-C chemokine receptor type 5 (CCR5) 2.CCR5 messenger RNA(CCR5 mRNA) |
10 |
Cobicistat |
|
Inhibitor of cytochrome P450 3A (CYP3A) enzymes |
11 |
Stavudine triphosphate |
|
Nucleoside analogue reverse transcriptase inhibitor used in the treatment of HIV infection |
Zahra Sheybani, Maryam Heydari Dokoohaki, Manica Negahdaripour, Mehdi Dehdashti, Hassan Zolghadr, Mohsen Moghadami, Seyed Masoom Masoompour, Amin Reza Zolghad
Submitted date: 26/03/2020 • Posted date: 30/03/2020 Licence: CC BY-NC-ND 4.0
Citation information: Sheybani, Zahra; Dokoohaki, Maryam Heydari; Negahdaripour, Manica; Dehdashti, Mehdi; Zolghadr, Hassan; Moghadami, Mohsen; et al. (2020): The Role of Folic Acid in the Management of Respiratory Disease Caused by COVID-19. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12034980.v1
Entrance of coronavirus into cells happens through the spike proteins on the virus surface, for which the spike protein should be cleaved into S1 and S2 domains. This cleavage is mediated by furin, which can specifically cleave Arg-X-X-Arg↓ sites of the substrates. Furin, a member of proprotein convertases family, is moved from the trans-Golgi network to the cell membrane and activates many precursor proteins. A number of pathological conditions such as atherosclerosis, cancer, and viral infectious diseases, are linked with the impaired activity of this enzyme. Despite the urgent need to control COVID-19, no approved treatment is currently known. Here, folic acid (folate), a water-soluble B vitamin, is introduced for the first time for the inhibition of furin activity. As such, folic acid, as a safe drug, may help to prevent or alleviate the respiratory involvement associated with COVID-19.
File List (1)
chemrxiv-COVID-19 manuscript-27320.pdf (1.38 MiB) |
|
Zahra Sheybani1,9, Maryam Heydari Dokoohaki2,9, Manica Negahdaripour3,4, Mehdi Dehdashti5, Hassan Zolghadr6, Mohsen Moghadami7, Seyed Masoom Masoompour7, and Amin Reza Zolghadr2,8*
Correspondence should be addressed to A. R. Z. (arzolghadr@shirazu.ac.ir); Tel: +98 713 613 7157, Fax: +98 713 646
0788, ORCID: 0000-0002-6289-3794 (A.R.Z).
Entrance of coronavirus into cells happens through the spike proteins on the virus surface, for which the spike protein should be cleaved into S1 and S2 domains. This cleavage is mediated by furin, which can specifically cleave Arg-X-X-Arg↓ sites of the substrates. Furin, a member of proprotein convertases family, is moved from the trans-Golgi network to the cell membrane and activates many precursor proteins. A number of pathological conditions such as atherosclerosis, cancer, and viral infectious diseases, are linked with the impaired activity of this enzyme.
Despite the urgent need to control COVID-19, no approved treatment is currently known. Here, folic acid (folate), a water-soluble B vitamin, is introduced for the first time for the inhibition of furin activity. As such, folic acid, as a safe drug, may help to prevent or alleviate the respiratory involvement associated with COVID-19.
Keywords: Coronavirus, 2019 novel coronavirus, Furin, Folic acid, Spike protein
Coronaviruses, a family of Coronaviridae, can cause significant human pathologies such as respiratory tract infections in humans and other mammals.1 Coronavirus infections are usually mild, but some beta coronaviruses including Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) may induce critical symptoms.2,3
In December 2019, an outbreak of lower respiratory tract infections was reported in Wuhan, China.4 The pathogen was recognized as a novel RNA beta coronavirus, later named as SARS-CoV-2.5 The infection caused by this virus, COVID-19, is declared by the World Health Organization (WHO) as a pandemic.6 In view of SARS-CoV-2 novelty, further researches are required to obtain more insights about its pathogenesis.
Coronavirus (CoV) genome encodes four structural proteins, comprising spike (S), membrane (M), envelope (E), and nucleocapsid (N). The spike (S) protein of coronaviruses mediates receptor binding and fusion of the virus with the target cells.7 Each class of coronavirus attaches to a specific cellular receptor to facilitate virus entrance into cells. Angiotensin- converting enzyme 2 (ACE2) and CD209L are shown responsible for SARS-CoV entrance.8-9 It is reported that SARS-CoV-2 enters the respiratory tract by interacting with ACE2 receptor.10
The spike protein comprises an amino (N)-terminal S1 subunit and a carboxyl (C)-terminal S2 subunit. The entrance of the virus is facilitated by cleavage of S protein to S1/S2 subunits. The S1 subunit binds to the ACE2 receptor, while the S2 site interacts with the cell membrane to mediate receptor-dependent endocytosis11, as shown in Fig1a. The coronavirus spike protein is cleaved into S1 (receptor binding subunit) and S2 (membrane fusion subunit) by a proteolytic activation at the furin consensus motif RRRR537↓S (R=arginine, ↓: cleavage site) in virus-infected cells. Additionally, the S2 subunit of the S protein is further cleaved at the second furin site (RRRR690↓S) in the infected cells expressing S constructs.12-16 Mutations of one basic residue in the RRRR690↓S motif and use of non-furin cleavable PRRR↓S sequence demonstrated that furin may play an important role in furin-dependent entry.17 The working protease is a cellular proprotein convertase that circulates between plasma membrane, early endosome, and trans- Golgi network (TGN), by participation in endocytic and exocytic paths.18,19 This proprotein convertase is a major candidate for processing the surface glycoproteins of pathogenic
viruses.20,21 Furin can cleave precursor proteins with specific motifs to produce mature proteins with biological activity. The first (P1) and fourth (P4) amino acids at the N-terminus of the substrate cleavage site must be arginine "Arg-X-X-Arg ↓" (R-X-X-R, X= any amino acid, ↓: cleavage site). If the P2 position is basic lysine or arginine, the cleavage efficiency could be improved by about 10 times.22 The results of a series of analyses have proposed that one of the important reasons for the high infectivity of COVID-19 is a redundant furin cut site in the virus spike protein.23
Our aim is to suggest folic acid as a potential inexpensive, safe, and non-immunogenic drug candidate for the prevention or treatment of early stages of respiratory disease associated with COVID-19 (Fig. 1). Folic acid is a type of B vitamin normally found in foods such as spinach, broccoli, asparagus, dried beans, lentils, peas, and oranges. Folic acid helps the body produce and maintain new cells and also prevent changes to DNA that may lead to cancer. Noticeably, folic acid deficiency is associated with a variety of human malignancies, including colorectal cancer. The over-expression of folate receptors in the early stages of malignant cell formation can be due to folic acid deficiency. Besides, folate malnutrition can cause a high incidence of adenomatous polyps and premalignant lesions of the colon.24 To this aim, the molecular dynamics (MD) simulations of the interactions of furin enzyme with folic acid and one of its active metabolites, folinic acid, was performed here for the first time to evaluate the interplay of these molecules with furin.
Fig. 1- A schematic representation of inhibitory action of folic acid. a, The mechanism of fusion and replication of COVID-19 virus. b, Inhibition of furin protein by folic acid.
The ligand-furin docking was performed to predict the major binding sites of folic acid and folinic acid molecules in the active site of furin protein. In general, the interaction energies between protein and ligands are obtained by docking studies. The obtained binding free energies
were -161.6, and -159.2 kcal/mol for folic acid and folinic acid, respectively. The results showed that folic acid and folinic acid molecules interacted well with the active site residues of furin by formation of hydrogen bonds. Different atom sites of the two drug molecules established hydrogen bonding interactions with various amino acids of furin as shown in Fig. 2a. Interestingly, the binding sites of folinic acid and furin were clearly different. The interactions of Gly307, Glu271, Tyr313, Gln488, Ala532, Arg490, and Asp530 residues with hydrogen, oxygen, and nitrogen atoms of folic acid were dominant; whereas, strong hydrogen bonds were established through Ser311, Glu271, Arg490, Lys449, and Gln488 residues of folinic acid molecules. Moreover, while the H19 and H12 atoms of folic acid interacted substantially with Glu271, the H2 and H4 atoms of folinic acid formed hydrogen bonds with the Glu271 residue of furin. These findings proposed different orientation preferences of folic acid and folinic acid molecules in the binding site of furin.
Fig. 2- Hydrogen bond interactions of drugs with furin. a, folic acid. b, folinic acid.
The MD simulations of folate derivatives interaction with furin were also conducted to gain additional insight into the specific mechanism by which folic acid and folinic acid molecules can exert their potential inhibitory actions in the furin active sites of COVID-19 patients. Atoms labeling for the two drug molecules under study are shown in Fig 3a. The snapshots of the simulated systems after 100 ns (water molecules were removed for clarity) are depicted in Fig. 3b. The position and orientation of drug molecules in the simulations are in line with docking results. The intermolecular interactions between different residues of furin and drug molecules.
Fig. 3 | MD simulation results. a, The chemical structures of drug molecules with atoms labeling. b, One mode of drugs binding to the furin protein taken from a snapshot of the simulation at 100 ns. Water molecules were removed for clarity. c, Comparison of RDFs between the centers of mass of some residues of furin with drugs (top panel) and the atom…atom RDFs (bottom panel) for systems contain: folic acid (left panel), folinic acid (right panel).
The radial distribution functions (RDFs) between furin’s residues and drug molecules are shown in Figs. 3c. For clarity, visual inspection of interaction sites are also demonstrated in Fig. 4 (see Fig. 3a for atom’s labels). To obtain statistically reliable structural data, RDFs are calculated by averaging over trajectories of long production runs. The RDFs between the center of mass of folic acid and different amino acids of furin indicates that Ala532, Tyr313, and Glu271 interacted with folic acid with a relatively high probability and small dynamics both at short and long distances. In this case, the atom…atom RDFs demonstrated that position of the first peak obtained for H19…O(Glu271) and O3…H(Tyr313) were smaller than that of O4…H(Ala532). Interestingly, MD simulations showed that the distance of O3 atom of folic acid with Tyr313 and Gln488 hydrogen atoms were calculated to be 1.66 Å, and 1.96 Å, respectively (see Fig. 3a for atom labeling and Fig. 4a). The main interaction of O4 atom of folic acid with Ala532, was located at 1.97 Å. The RDF peaks in Fig. 3c (right panel) showed that the folinic acid tended positioning slightly towards Ser311, Glu271, Arg490, Gln488, and Lys499 at short and long ranges. As shown in Fig. 4b, the main atomic interactions in this case were H2…O(Glu271), and N5…H(Ser311), which were located at 1.97 Å.
More details can be obtained from the spatial distribution function of the hydrogen bonding between the furin’s amino acids and different atom sites of the drug molecules by the calculation of combined radial/angular distribution function (CDF) as a powerful tool for defining hydrogen bond criteria. Fig. 4c (up panel) manifests the most favorable hydrogen bonding interaction between the polar hydrogen atoms of the Tyr313 and the O3 atom of carbonyl group of folic acid in the angle range 170 < 𝜃 < 180 at the distance of around 1.66 Å. Particularly, the CDF of Fig. 4c (down panel) indicates that there are interactions between the hydroxyl group of Ser311 and the folinic acid with the angle range 170 < 𝜃 < 180 and 1.97 Å distance. These interactions occurred when the drug molecules tilted substantially to directly interact with furin. Based on these findings, the folic acid…furin interactions were more probable than folinic acid.
Fig. 4 | The main interaction of drugs with different residues of furin. a, Folic acid. b, Folinic acid. Drug molecules and residues are represented with sticks. For drugs, the red, blue, pink and white atom sites represent the oxygen, nitrogen, carbon, and hydrogen atoms. For amino acids of furin, the carbon atoms are colored in green. c, CDF of (up panel) furin-folic acid, (down panel) furin-folinic acid systems.
Objective: This study aimed to investigate the potential parameters associated with imaging progression on chest CT from coronavirus disease 19 (COVID-19) patients. Results: The average age of 273 COVID-19 patients enrolled with imaging progression were older than those without imaging progression (p = 0.006). The white blood cells, platelets, neutrophils and acid glycoprotein were all decreased in imaging progression patients (all p < 0.05), and monocytes were increased (p = 0.025). The parameters including homocysteine, urea, creatinine and serum cystatin C were significantly higher in imaging progression patients (all p < 0.05), while eGFR decreased (p < 0.001). Monocyte-lymphocyte ratio (MLR) was significantly higher in imaging progression patients compared to that in imaging progression-free ones (p < 0.001). Logistic models revealed that age, MLR, homocysteine and period from onset to admission were factors for predicting imaging progression on chest CT at first week from COVID-19 patients (all p < 0.05). Conclusion: Age, MLR, homocysteine and period from onset to admission could predict imaging progression on chest CT from COVID-19 patients. Methods: The primary outcome was imaging progression on chest CT. Baseline parameters were collected at the first day of admission. Imaging manifestations on chest CT were followed-up at (6±1) days.
Since the end of 2019, a novel coronavirus with person-to-person transmission has spread to many other countries worldwide [1–5]. Previous epidemiology report uncovered that the epidemic of coronavirus disease 2019 (COVID-19) has doubled every 7.4 day in its early stage, with an average serial interval of 7.5 days [3]. Early information estimated that the basic reproductive number R0 was estimated to be 1.4 – 2.5 reported by WHO [2]. The pandemic is accelerating at an exponential rate and at risk of escalating into a global health emergency [2]. The mortality of coronavirus disease 2019 (COVID-19) patients in China is approximately 2.3%, compared with 9.6% of severe acute respiratory syndrome (SARS) and 34.4% of middle east respiratory syndrome (MERS) reported by WHO [6]. Even this virus is not as fetal as people thought, the transmissibility is far exceeding that of SARS and MERS [7]. Although many clinical and epidemiological literatures have been published [3–6, 8–10], the spread in still ongoing and the early warning parameters for disease progression remain incomplete.
Compared to symptoms, chest CT findings were more rapid and frequent [11, 12]. The imaging performance on chest CT scans from COVID-19 patients mainly manifested as bilateral ground-glass opacities (GGOs) in the lung periphery [13]. In a retrospective cohort, chest CTs of 121 symptomatic COVID-19 patients have been reviewed. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%) [11]. Currently, chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia [14]. In a cohort study, 85.7% (54/63) confirmed COVID-19 patients developed imaging progression including enlarged and increased extent of GGOs and consolidation at early follow-up chest CT scans [12]. That is, short-term imaging progression on chest CT from COVID-19 patients should be early predicted and intervened.
Imaging performance of progression and progression-free patients
As shown in Figure 1, most mild type COVID-19 patients had bilateral and peripheral GGOs, consolidation and linear opacities imaging involvements on chest CT at the first admission day. Some patients had no remarkable hallmarks. At the first six (±1) day, enlarged and increased GGOs, consolidation, solid nodules and fibrous stripes were observed for patients suffered from imaging progression on chest CT scans. On the contrary, the GGOs, consolidation and linear opacities were partly resolved and decreased for imaging progression-free patients.
Baseline characteristics and inflammatory model comparisons between imaging progression and progression-free patients
In total, 71 COVID-19 patients suffered from imaging progression on chest CT at first week after admission, and the other 202 patients were imaging progressionfree on chest CT. As summarized in Table 1, the patients in imaging progression group were significantly older than those in imaging progressionfree group (p = 0.006, Table 1). More patients were treated with gamma globulin and thymosin in imaging progression group compared to those without imaging progression (p = 0.022 and p = 0.001, respectively, Table 1). In blood routine tests, the white blood cells (WBC), platelets and neutrophils were significantly lower in imaging progression patients than those in imaging progression-free ones (p = 0.025, p = 0.044 and p = 0.014, respectively, Table 1), while the monocytes were significantly higher in imaging progression patients (p = 0.025, Table 1). Additionally, acid glycoprotein was significantly lower in imaging progression patients (p = 0.037, Table 1). In liver function tests, gamma-glutamyl transferase (GGT) levels were significantly higher in imaging progression-free patients (p = 0.045, Table 1), while homocysteine levels were significantly higher in imaging progression patients (p = 0.006, Table1). In kidney function tests, urea, creatinine and serum cystatin C levels were significantly higher in imaging progression patients compared to those in imaging progression-free ones (p = 0.011, p = 0.007, respectively, Table 1). As we expected, the estimated glomerular filtration rate (eGFR) levels were significantly decreased in imaging progression patients (p < 0.001, Table 1). No differences were found in cardiac markers and coagulation function tests.
Co-manifestations on chest CT and outcomes
As summarized in Table 2, except for common manifestations on chest CT, chronic inflammatory
manifestation, chronic bronchitis / emphysema, pericardial effusion, pleural effusion, bullae of lung and obsolete tuberculosis were the most frequent imaging co-manifestations in COVID-19 patients. COVID-19 patients with imaging progression had significantly higher frequency of chronic inflammatory manifestation than those without imaging progression (12.7% vs. 3.5%, p = 0.005, Table 2). No differences were found in distributions of chronic bronchitis / emphysema, pericardial effusion, pleural effusion, bullae of lung and obsolete tuberculosis between these two groups (Table 2).
Parameters associated with imaging progression on chest CT
Variables including age, gender, disease history, epidemiology, chest CT imaging, therapeutic strategies, period from onset to admission, ALRI, APRI, MLR, NLR, PLR, SII, WBC, neutrophils, lymphocytes, monocytes, platelet, red blood cells (RBC), hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), GGT, lactate dehydrogenase (LDH), total bilirubin (TBiL), albumin, globulin, urea, creatinine, eGFR, lactic acid, haptoglobin, acid glycoprotein, cystatin C, homocysteine, retinolbinding protein, cardiac troponin (cTnI), myoglobin, brain natriuretic peptide prohormone (pro-BNP), prothrombin time, prothrombin activity (PTA), international normalized ratio (INR), D-dimer were included in the univariate analysis. As presented in Table 3, age, gamma globulin therapy, thymosin therapy, MLR, serum cystatin C, homocysteine, eGFR and period from onset to admission were potential parameters associated with imaging progression (all p < 0.05, Table 3). When these parameters were included in the multivariate model, age, MLR and homocysteine were significantly correlated with imaging progression on chest CT from COVID-19 patients (RR = 2.28, 95%CI = 1.12 – 4.34, p = 0.012; RR = 7.69, 95%CI = 1.67 – 35.55, p = 0.009 and RR = 3.17, 95%CI = 1.01 – 9.96, p = 0.048; respectively, Table 3). In addition, COVID-19 patients with period from onset to admission ≥ 4 days might have lower risk to develop imaging progression on chest CT at first week after admission (RR = 0.35, 95%CI = 0.19 – 0.67, p = 0.001, Table 3).
Moreover, no acute bacterial or other viral co-infection performances on chest CT were found in these COVID19 patients.
All these COVID-19 patients did not develop severe conditions, no one died during our follow up.
Parameters associated with imaging progression on chest CT
Variables including age, gender, disease history, epidemiology, chest CT imaging, therapeutic strategies, period from onset to admission, ALRI, APRI, MLR, NLR, PLR, SII, WBC, neutrophils, lymphocytes, monocytes, platelet, red blood cells (RBC), hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), GGT, lactate dehydrogenase (LDH), total bilirubin (TBiL), albumin, globulin, urea, creatinine, eGFR, lactic acid, haptoglobin, acid glycoprotein, cystatin C, homocysteine, retinolbinding protein, cardiac troponin (cTnI), myoglobin, brain natriuretic peptide prohormone (pro-BNP), prothrombin time, prothrombin activity (PTA), international normalized ratio (INR), D-dimer were included in the univariate analysis. As presented in Table 3, age, gamma globulin therapy, thymosin therapy, MLR, serum cystatin C, homocysteine, eGFR and period from onset to admission were potential parameters associated with imaging progression (all p < 0.05, Table 3). When these parameters were included in the multivariate model, age, MLR and homocysteine were significantly correlated with imaging progression on chest CT from COVID-19 patients (RR = 2.28, 95%CI = 1.12 – 4.34, p = 0.012; RR = 7.69, 95%CI = 1.67 – 35.55, p = 0.009 and RR = 3.17, 95%CI = 1.01 – 9.96, p = 0.048; respectively, Table 3). In addition, COVID-19 patients with period from onset to admission ≥ 4 days might have lower risk to develop imaging progression on chest CT at first week after admission (RR = 0.35, 95%CI = 0.19 – 0.67, p = 0.001, Table 3).
Variables |
Chest CT Progression group (n = 71)
|
Chest CT Progression-free group (n = 202) |
p-value |
Age, years, mean ± SD | 53.5 ± 1.9 | 47.6 ± 1.1 | 0.006 |
Male, n (%) | 33 (46.5) | 101 (50) | 0.61 |
Disease history, n (%) | |||
None | 48 (67.6) | 143 (70.8) | |
Hypertension | 13 (18.3) | 27 (13.4) | |
Diabetes | 7 (9.9) | 11 (5.4) | |
Fatty liver disease | 12 (16.9) | 27 (13.4) | |
Others | 3 (4.2) | 21 (10.4) | |
Epidemiology, n (%) | |||
Hubei sojourning history | 43 (56.3) | 108 (53.5) | 0.301 |
Contact with COVID-19 patients | 27 (38.0) | 72 (35.6) | 0.719 |
Therapeutic strategy, n (%) | |||
Antivirus drugs | 58 (81.7) | 141 (69.8) | 0.053 |
Antibiotics | 22 (31.0) | 46 (22.8) | 0.169 |
Gamma globulin | 13 (18.3) | 17 (8.4) | 0.022 |
Thymosin | 20 (28.2) | 23 (11.4) | 0.001 |
Glucocorticoid | 10 (14.1) | 17 (8.4) | 0.169 |
TCM decoction | 5 (7.0) | 25 (12.4) | 0.216 |
TCM patent | 27 (38.0) | 58 (28.7) | 0.145 |
Chest CT imaging, n (%) | |||
Bilateral lung lesion | 60 (84.5) | 177 (87.6) | |
Single lung lesion | 11 (15.5) | 25 (12.4) | |
Blood routine tests, mean ± SD | |||
WBC, 103/mm3 | 4.6 ± 0.1 | 5.2 ± 0.1 | 0.025 |
RBC, 104/mm3 | 4.4 ± 0.1 | 4.5 ± 0.04 | 0.334 |
Hemoglobin, g/L | 135.1 ± 1.7 | 136.7 ± 1.1 | 0.465 |
Platelet, 103/mm3 | 176.0 ± 6.6 | 195.0 ± 5.1 | 0.044 |
Neutrophils, 103/mm3 | 2.9 ± 0.1 | 3.5 ± 0.1 | 0.014 |
Lymphocytes, 103/mm3 | 1.2 ± 0.1 | 1.3 ± 0.04 | 0.342 |
Monocytes, 103/mm3 | 0.5 ± 0.03 | 0.4 ± 0.01 | 0.025 |
Hypersensitive CRP, mg/L, mean ± SD | 17.5 ± 2.4 | 18.7 ± 1.6 | 0.697 |
ESR, mm/Hour, mean ± SD | 56.9 ± 4.3 | 64.5 ± 2.7 | 0.148 |
Procalcitonin, ng/ml, mean±SD | 0.05 ± 0.01 | 0.09 ± 0.05 | 0.687 |
Acid glycoprotein, mg/dl, mean ± SD | 140.9 ± 5.6 | 154.5 ± 3.3 | 0.037 |
Liver function tests, mean ± SD | |||
ALT, U/L | 27.6 ± 2.3 | 27.6 ± 1.4 | 0.995 |
AST, U/L | 29.4 ± 1.7 | 29.2 ± 1.6 | 0.958 |
GGT, U/L | 29.5 ± 2.5 | 38.6 ± 2.5 | 0.045 |
LDH, U/L | 244.4 ± 10.4 | 248.8 ± 5.8 | 0.703 |
TBiL, μmol/L | 8.4 ± 0.4 | 9.2 ± 0.3 | 0.116 |
Albumin, g/L | 40.8 ± 0.4 | 41.1 ± 0.3 | 0.537 |
Globulin, g/L | 28.8 ± 0.5 | 29.0 ± 0.3 | 0.693 |
Homocysteine, μmol/L | 10.7 ± 0.5 | 9.3 ± 0.2 | 0.006 |
Renal function test, mean ± SD | |||
Urea, mmol/L | 5.1 ± 0.2 | 4.5 ± 0.1 | 0.011 |
Creatinine, μmol/L | 70.7 ± 3.0 | 63.0 ± 1.3 | 0.007 |
Serum cystatin C, mg/L | 1.0 ± 0.04 | 0.8 ± 0.01 | < 0.001 |
eGFR, ml/(min×1.73m2) | 101.3 ± 3.1 | 116.3 ± 1.9 | < 0.001 |
Lactic acid, mmol/L, mean ± SD | 2.8 ± 0.1 | 2.8 ± 0.04 | 0.936 |
Haptoglobin, mg/dl, mean ± SD | 209.2 ± 12.0 | 229.6 ± 7.0 | 0.142 |
Retinol-binding protein, mg/L, mean ± SD 27.8 ± 1.4 26.4 ± 0.7 0.327 Cardiac markers, mean ± SD | 27.8 ± 1.4 | 26.4 ± 0.7 | 0.327 |
cTnI, ng/ml | 0.029 ± 0.004 | 0.033 ± 0.003 | 0.455 |
Myoglobin, ng/ml | 17.5 ± 3.0 | 14.7 ± 2.9 | 0.59 |
Pro-BNP, pg/ml | 73.5 ± 13.7 | 67.6 ± 7.2 | 0.692 |
Coagulation function tests, mean ± SD | |||
INR | 1.01 ± 0.008 | 1.02 ± 0.008 | 0.424 |
PTA | 99.9 ± 1.2 | 99.0 ± 0.8 | 0.579 |
Prothrombin time, second | 13.4 ± 0.08 | 13.5 ± 0.08 | 0.402 |
D-Dimer, μg/ml | 0.55 ± 0.06 | 0.77 ± 0.11 | 0.254 |
Table 3. parameters associated with imaging progression in chest CT from COVID-19 patients#.
Variables |
Univariate RR |
Univariate 95%CI |
p value |
Multivariate RR |
Multivariate 95%CI |
p value |
Age, years | ||||||
<60 | reference | - | 1.0 | reference | - | 1.0 |
≥60 | 2.72 | 1.55-4.78 | < 0.001 | 2.28 | 1.12-4.34 | 0.012 |
Gamma globulin, yes vs. no | 2.44 | 1.12-5.32 | 0.025 | 1.08 | 0.38-3.08 | 0.89 |
Thymosin, yes vs. no | 3.05 | 1.55-6.0 | 0.001 | 2.32 | 0.94-5.73 | 0.069 |
MLR, per increase 1 unit | 12.2 | 3.09-48.23 | < 0.001 | 7.69 | 1.67-35.55 | 0.009 |
Serum cystatin C, mg/L | ||||||
< 1.03 | reference | - | 1.0 | reference | - | 1.0 |
> 1.03 | 2.8 | 1.35-5.82 | 0.006 | 0.79 | 0.28-2.2 | 0.65 |
Homocysteine, μmol/L | ||||||
< 15.4 | reference | - | 1.0 | reference | - | 1.0 |
> 15.4 | 3.54 | 1.23-10.14 | 0.019 | 3.17 | 1.01-9.96 | 0.048 |
eGFR, ml/(min×1.73m2) | ||||||
> 90 | reference | - | 1.0 | reference | - | 1.0 |
< 90 | 2.97 | 1.54-5.75 | 0.001 | 1.63 | 0.67-4.0 | 0.281 |
Period from onset to admission, days | ||||||
< 4 | reference | - | 1.0 | reference | - | 1.0 |
≥ 4 | 0.36 | 0.20-0.64 | 0.001 | 0.35 | 0.19-0.67 | 0.001 |
TCM, Traditional Chinese Medicine; WBC, white blood cells; RBC, red blood cells; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; LDH, lactate dehydrogenase; TBiL, total bilirubin; eGFR, estimated glomerular filtration rate; cTnI, cardiac troponin; Pro-BNP, Brain natriuretic peptide prohormone; INR, international normalized ratio; PTA, prothrombin activity.
Co-manifestations, n (%) |
Chest CT Progression Group (n = 71) |
Chest CT Progression-Free Group (n = 202) |
p-value |
Chronic inflammatory manifestations |
9 (12.7) | 7 (3.5) | 0.005 |
Chronic bronchitis / emphysema | 2 (2.8) | 2 (1.0) | 0.271 |
Pericardial effusion | 1 (1.4) | 1 (0.5) | 0.438 |
Pleural effusion | 1 (1.4) | 0 (0) | 0.091 |
Bullae of lung | 1 (1.4) | 2 (1.0) | 0.771 |
Obsolete tuberculosis | 2 (2.8) | 1 (0.5) | 0.107 |
Variables |
Univariate RR |
Univariate 95%CI |
p value |
Multivariate RR |
Multivariate 95%CI |
p value |
Age, years | ||||||
<60 | reference | - | 1.0 | reference | - | 1.0 |
≥60 | 2.72 | 1.55-4.78 | < 0.001 | 2.28 | 1.12-4.34 | 0.012 |
Gamma globulin, yes vs. no | 2.44 | 1.12-5.32 | 0.025 | 1.08 | 0.38-3.08 | 0.89 |
Thymosin, yes vs. no | 3.05 | 1.55-6.0 | 0.001 | 2.32 | 0.94-5.73 | 0.069 |
MLR, per increase 1 unit | 12.2 | 3.09-48.23 | < 0.001 | 7.69 | 1.67-35.55 | 0.009 |
Serum cystatin C, mg/L | ||||||
< 1.03 | reference | - | 1.0 | reference | - | 1.0 |
> 1.03 | 2.8 | 1.35-5.82 | 0.006 | 0.79 | 0.28-2.2 | 0.65 |
Homocysteine, μmol/L | ||||||
< 15.4 | reference | - | 1.0 | reference | - | 1.0 |
> 15.4 | 3.54 | 1.23-10.14 | 0.019 | 3.17 | 1.01-9.96 | 0.048 |
eGFR, ml/(min×1.73m2) | ||||||
> 90 | reference | - | 1.0 | reference | - | 1.0 |
< 90 | 2.97 | 1.54-5.75 | 0.001 | 1.63 | 0.67-4.0 | 0.281 |
Period from onset to admission, days | ||||||
< 4 | reference | - | 1.0 | reference | - | 1.0 |
≥ 4 | 0.36 | 0.20-0.64 | 0.001 | 0.35 | 0.19-0.67 | 0.001 |
|
Estimate |
95%CI |
MLR |
|
|
Cutoff |
0.51 |
- |
Sensitivity |
0.44 |
0.32 – 0.56 |
Specificity |
0.79 |
0.72 – 0.84 |
Positive predictive value |
0.42 |
0.34 – 0.54 |
Negative predictive value |
0.80 |
0.71 – 0.85 |
Age, years |
|
|
Cutoff |
51 |
- |
Sensitivity |
0.65 |
0.53 – 0.76 |
Specificity |
0.58 |
0.51 – 0.65 |
Positive predictive value |
0.35 |
0.29 – 0.48 |
Negative predictive value |
0.83 |
0.74 – 0.86 |
Homocysteine, μmol/L |
|
|
Cut off |
10.58 |
|
Sensitivity |
0.42 |
0.31 – 0.55 |
Specificity |
0.79 |
0.72 – 0.84 |
Positive predictive value |
0.41 |
0.33 – 0.53 |
Negative predictive value |
0.80 |
0.70 – 0.85 |
If you’ve been in the pharmacy area of any national grocery store or drugstore in the last few years, you may have noticed: there is a truly overwhelming variety of vitamins and supplements out there on the market. Not only are there competing brands (which is good), but then you get to choose your flavor, your texture, your method of taking it (chewable, powder, pill), “all natural” or not, and then you can decide whether you want a specialized vitamin for:
And so on.
And that’s just at the chain stores. What about specialty shops, niche markets...companies like us? The options are staggering.
So what do you really need to know when trying to choose a multivitamin?
We’ll explain.
Research shows that the best way to intake the vitamins and minerals necessary for good health is through diet. Naturally occurring vitamins, such as folate in spinach, are more readily absorbed by a healthy body than those present in synthetic forms. Plus, when you eat nourishing foods, you get all the other benefits that food has to offer. In populations where healthy food is accessible, most people get an adequate supply of vitamins and minerals through their diet. Those are often the same people who are conscious about taking multivitamins, so they’re doubling up unnecessarily.
BUT--someone who has a condition or who takes medicine that hinders or blocks absorption of nutrients is not, for our purposes, “most healthy people.” And there are actually scores of people who fall into this category, among them being people with Celiac, Crohn’s, alcoholism, people going through chemo, taking metformin or warfarin (to name a few)
and the multitudes of others with MTHFR issues. YOU NEED VITAMIN SUPPLEMENTS, because even if you eat healthy foods, your body isn’t getting the full benefit because it’s malfunctioning on some major biopathways.
If you check the back of the bottle of vitamins, you’ll see a column that says “Amount Per Serving,” and “Percent (%) Daily Value.” These matter. The dosage of nutrients should meet your needs, but not exceed the recommended amounts, because with many vitamins, like Vitamins C, B3 (Niacin) or Zinc, it’s very possible to have too much of a good thing.
Your immune system is your body’s defense mechanism against various different illnesses, infections, and diseases. It knows what cells are vital to the body’s function while working to eliminate anything that’s unwanted.
With the COVID-19 outbreak causing widespread panic around the world, the most effective thing we can do for our bodies during this time is to take care of it in the best ways we know how. With proper awareness and a proactive attitude, we can fight through this and return to the life we’ve grown accustomed to.
If you’re like the rest of the population and are trying to find ways to boost your immune system, you’ve probably come across a wide range of conflicting arguments. We’ve noticed a lot of inaccurate information floating around, and we wanted to set the record straight on some proven ways to boost our infamous immune system.
Although our bodies require all vitamins and minerals to function properly, there’s one that has gained a lot of attention since the coronavirus outbreak began -- Vitamin D. When taken in moderate doses which keep your Vitamin D blood levels up, your immune system will utilize Vitamin D when fighting off viruses.
One of the easiest ways to get Vitamin D is through sunlight, believe it or not. While we should be practicing social distancing, that doesn’t mean you should be staying inside all day. Enjoy some sunlight and ensure you’re consuming enough Vitamin D throughout the day (fatty fish, eggs, cheese, mushrooms). If you are in a cloudy area of the world (or don’t have as much access to direct sunlight), consider supplementing with D3 specifically, approximately 2,000 - 5,000 IUs daily.
Zinc is one of the natural virus killers when it’s found in abundance in the bloodstream or other places where viruses like to replicate (like the throat, etc.). It can help slow a virus from replicating when it’s present, though once a virus gets into the cells, zinc has trouble getting transported into the cell where it can then defeat the virus. This is where the hydroxychloroquine or Plaquenil is actually used as the transport to get the zinc into the cells to kill the Coronavirus. This is why this old drug is getting so much new attention amidst this COVID-19 pandemic. But if you’re taking a good 15-20 mg of zinc each day, preventatively, your immune system will definitely thank you for the extra help!
Our sleeping patterns play a large role in our ability to stay healthy. Our body uses this time for critical recovery and to repair a variety of functions -- your immune system included. For those that aren’t getting the recommended 7-9 hours per night, it’s possible your body doesn’t have the time to recover properly, leaving you prone to sickness.
This is another way of improving your immune system without spending any money. Exercise is known to support infection-fighting cells, while also reducing inflammation in the body. All you need is a solid 30 minutes of exercise every day!
Whether you choose to go for a walk, run, or do some bodyweight exercises in your living room, always save enough time for some form of physical activity every day. Your body will thank you!
And if you can’t exercise due to various health challenges, consider taking a sauna if you have a home unit. There are some amazing studies out of Finland about long-term health in relation to saunas. Not only that, you evoke some great detoxification in the body and stimulate wonderful circulation, both great contributors to general health and the immune system.
If you don’t have a home sauna but are interested in considering one, check out our favorite local Canadian company with a USA-based warehouse. They have an amazing line of superior saunas. Right now they’ve not only got great technology superseding all others in the marketplace but have phenomenal entry-level pricing. They are the only saunas that actually test with the lowest EMF/ELF on the market (all saunas market this fact, but when you actually put them to the test with a device, very few can deliver on these claims after the sale when a real testing unit is leveraged). Tell them Methyl-Life sent you and they’ll treat you right.
In the wake of the coronavirus outbreak, maintaining a healthy body and an effective immune system has never been more important. With the right habits, we can find a way to get through this and eventually work our way back into a more normal quality of life.
We’ve all heard about the sanitary concerns that we need to take into consideration daily.
Washing our hands conscientiously, having hand sanitizer handy, avoiding contact with your face, keeping a safe distance from others, and maintaining a clean home are some of the best ways to keep the coronavirus away from you and your family.
In addition to paying more attention to our sanitation, this is a great opportunity to finally take control of your other lifestyle habits that will help you stay coronavirus-free. Since our immune system will play a large role in fighting off disease, maintaining a healthy diet will be just as important as keeping a clean home.
Many of us are going to have a lot of “home” time on our hands during the lockdown. This should eliminate many excuses we tend to make about not paying attention to our daily nutrition and diet.
While we don’t know how long we’ll be dealing with a lockout, taking control of our health now will make us stronger people by the time we’ve moved into a safer place.
Histamine also has a few other important functions in the bowel and is also known to act as a neurotransmitter (chemical messenger). It’s also involved in the secretion of gastric acid, inflammation, and the regulation of vasodilation and bronchoconstriction.
If you’re like most people and are still trying to figure out how to maintain a healthy diet during these tough times, we have some advice to help make this much easier for you and your family.
Let’s take a look at our biggest tips for staying healthy during the coronavirus lockdown:
Do things that bring joy (believe it or not, this actually positively affects the immune system) - laugh out loud, plan a dance party, enjoy with your pet, relax, play a game, express yourself (paint/draw/write/etc.), connect with those you love.
While many of us are dealing with major life changes right now, this is the perfect chance to rid yourself of all the negative habits you’ve accrued over the years.
With a more positive attitude, a healthier body, a stronger immune system, and improved habits, we can find a way to beat this.
Multivitamins can be an excellent addition to anyone’s diet and nutritional regimen, especially to people who don’t eat certain nutrient-rich foods or have allergies that prevent them from certain foods.
When properly taken, a multivitamin will assist your body in getting all the nutrients it needs throughout the day. This is essential to ensuring our bodies function adequately and properly 24/7 -- even when we’re sleeping!
While these tablets or capsules can do so much for you in the long run, and there are some things you might notice once you start taking them for the first time. Some of these things might scare people away at first, but it’s important to know what’s normal and what’s not.
If you’ve just started to experiment with multivitamins, you can expect to experience the following in the coming days and weeks as your body gets used to the nutritional change.
One of the vital functions a majority of vitamins play is converting the food we eat into energy. When we increase our vitamin intake from what we’re used to receiving, there’s a good chance that you’ll feel much more energetic throughout the day.
Your body will eventually get used to the added energy and it will become your new normal. You might even be surprised at how little energy you had before (if you forget to take your vitamins, you can get reminded of this). You’ll definitely be grateful to know that you’re now getting all that extra energy every single day.
Nausea is a side-effect for some people that just start taking a new vitamin or multivitamin. Most of the time, this is simply due to our body adjusting to the higher levels. Other times, it could be due to taking the vitamin on an empty stomach or taking too much of one vitamin. For example, taking most forms of zinc on an empty stomach can cause nausea. Consider trying a coated form like Sucrosomial® zinc.
Not getting the necessary amount of each essential nutrient every day won’t allow your skin, muscles, hair, and joints to repair themselves correctly. When you start taking vitamins, you might notice your skin being much smoother and more radiant.
You’ll also notice you’re much stronger now that you have increased energy and better function throughout your body. You’d be surprised at how much your nutrient deficiency has always shown itself -- you just didn’t know it.
Vitamins and minerals are essential micronutrients that our bodies need to function properly. While most of us will have no problem getting the necessary amounts through our normal diet, some of us will need the help of a vitamin supplement to reach our daily requirements.
In order to get the most out of your vitamin, you need to ensure you’re taking it properly and following the various directions for use. Research has found that taking too much of certain vitamins can have adverse effects on your body.
Other studies have shown that taking multiple vitamins and minerals will cause them to compete with each other -- meaning your body won’t absorb everything that you consume.
While there won’t necessarily be a “one-size fits all” solution for vitamins, there will be several universal guidelines you should follow when adding vitamins and multivitamins to your daily regimen.
The main rule of thumb when it comes to taking a vitamin properly is to refrain from using them as a replacement to getting the vitamins the old-fashioned way (through our diet). Vitamins should be used as the “side-kick” to your typical healthy eating habits and shouldn’t take away from that.
If you’re getting an adequate amount of vitamins and minerals already, there’s no need to take more. A majority of vitamins are going to be water-soluble and won’t get stored by the body, so any excess will just be excreted at a later time.
Also Read: Treating Anxiety Naturally & recognizing its Mechanism of Action within the body
When combining vitamins, there will be some that work better together than others. Here’s a quick breakdown of some things to keep in mind:
Before purchasing a vitamin, it’s always important to read the label to see what’s included in each serving. They’ll list the percentage of each nutrient in relation to your daily recommended amount, so you can easily see how much is in there.
For most vitamins, water will be an adequate drink to down them with since most of them are water-soluble. The fat-soluble vitamins will likely benefit most when taken with fatty foods or even milk.
If you’re interested in learning more about how to properly take a vitamin, contact us today and we’ll be happy to assist you!
Also Read: Folate, Vitamin B6, and Vitamin B12 Intake in Relation to Hyperuricemia
You’ve probably heard your family, doctors, or teachers tell you about the importance of vitamins and minerals in your diet. One question that gets asked often is whether these vitamins can do anything for weight loss.
The short answer is yes, but it’s also a complicated answer. While vitamins can play a role in losing weight, they do so indirectly and behind-the-scenes. For many people, vitamins will make a good “workout buddy” when trying to lose weight, but they won’t be able to achieve that feat alone.
With that being said, let’s explain a little further how multivitamins can help you lose weight.
If you’re trying to lose weight, your main goal is going to be burning more calories than you take in. There’s going to be a lot of working parts when trying to accomplish that. One thing that can help is improved metabolism.
Metabolism is just one of the many chemical reactions our body processes on a daily basis. Without this reaction, our body won’t convert proteins, fats, carbs, and other nutrients into energy. A faster metabolism means you’re burning calories at a quicker rate, which will, in turn, help you lose weight.
When you aren’t converting these nutrients into energy, they’ll be stored as fat -- that’s what you’re trying to avoid here. Since our metabolism naturally declines as we age, multivitamins become more and more necessary the older we get.
Also Read: Low Folate Levels and ADHD
There are a lot of different vitamins out there and they can be difficult to keep account of. Furthermore, a majority of them will help improve your metabolism in one way or another.
One of the most important vitamins for metabolism is Vitamin B, of which there are 8 to keep in mind -- B1, B2, B3, B5, B6, Folate, Biotin, B12. All of these will work together in converting proteins, carbs, and fats into energy.
The chemical reactions in our body wouldn’t be possible if it weren’t for magnesium -- making it another must-have vitamin when trying to lose weight. Iron is another popular vitamin that can help you lose weight. Iron helps transfer oxygen to your muscles. Without enough oxygen, your muscles won’t burn fat properly.
Vitamin D and Calcium have also been linked to weight loss, though research and studies are limited.
Also Read: How Methylfolate Affects Depression | How To Get Rid Of Depression
Vitamins can do a lot to help you lose weight, but they won’t do it by themselves. You will need to make some lifestyle changes in order to fully achieve your weight goals. This will be done through a balance of healthy dieting and exercising.
Mixing vitamins into your regimen will only enhance your bodily functions and allow you to perform at maximum capacity. You’ll be in a better mood, feel more alert, motivated, and your body will be rewarding you consistently throughout the day.
Magnesium is an essential part of our body’s chemical reactions. In fact, it’s essential to more than 300 biochemical reactions in our body that happen simultaneously. For those that are deficient in this mineral (and this is a large percentage of the population due to its lack in our current food supply), proper supplementation will be recommended.
What does magnesium do for us, anyway? Not only will it help convert food into energy, but it will aid in the creation of proteins, muscle movements, regulating neurotransmitters, and repairing/forming new DNA and RNA.
Outside of that, magnesium can indirectly help your athletic performance, fight depression, lower blood pressure, promote a healthy heartbeat, and has anti-inflammatory properties.
Studies show that nearly half of all Americans are deficient in magnesium or simply don’t get enough on a daily basis. If you’re trying to figure out how much magnesium you need on a daily basis, it will largely depend on your body type and gender.
Let’s take a look at what your goal should be every day:
It should be noted that these numbers will fluctuate as we grow older. When we hit the age of 30, we should increase our magnesium intake by 20 mg a day. Likewise, a pregnant woman will need 40 mg extra to support her baby.
The good news is our body will automatically excrete excess magnesium if necessary. The only downside of taking too much is the possibility of nausea, cramps or loose stool if you’re taking the citrate form -- not to mention wasting the magnesium when you excrete it.
Also Read: Well… How Much Should I Take? A Beginner’s Guide to Methylfolate Dosage
Magnesium is found in a variety of foods we eat on a daily basis, so if we’re diligent, we may be able to get the amount we need every day from our diets. We’ve listed some of the healthiest sources of magnesium and how much you can expect to get from them.
Outside of that, 1 cup of soy milk contains 61 mg of magnesium, ½ cup of black beans contains 60 mg, whole wheat bread will have 46 mg per 2 slices, and peanut butter will contain 49 mg per 2 tablespoons.
You can also get quality servings from edamame, avocado, rice, potatoes, yogurt, and oatmeal.
The first thing you should do when trying to figure out if magnesium supplementation is right for you is to see your doctor. They’ll be able to perform a blood test that can tell you whether or not you’re getting enough as it is.
If you are receiving enough, it’s best to continue your diet as you normally would. If not, taking a supplement can help your body store magnesium throughout the day. If you don’t get enough from your diet -- either because you don’t eat foods that contain it or don’t eat enough of them -- a supplement will be there to save the day.
Sleep: A wellness trend that is receiving a lot of attention these days. Why? Not only is sleep imperative for optimal health, but it is free and accessible to everyone. Getting adequate, restorative sleep has been known to help the body and brain clear waste and re-energize cells. Deep, recuperative sleep also helps the brain to consolidate memories.
Unfortunately, a vast majority of Americans are not getting an adequate amount of sleep each night, which can lead to a variety of health issues. Some side effects of sleep deprivation or inadequate sleep can include:
As the daytime hours fade away and evening approaches, your body should begin making more melatonin, a natural hormone that helps promote rest and rejuvenation. However, if cortisol levels are high at night (which can be due to a myriad of reasons, including stress, caffeine intake, or overstimulation), your body is not able to make and secrete adequate amounts of the melatonin hormone.
Magnesium is an important, abundant mineral in the body that supports the production of the “sleep hormone,” melatonin. If someone is deficient in magnesium, their body may have difficulty creating adequate amounts of melatonin needed for restful sleep.
Additionally, an adequate amount of magnesium in the human body is important for the normal functioning of the Central Nervous System. This system controls everything from our thoughts to our movements, emotions, and even our breathing. Magnesium is specifically known to aid this process by activating the parasympathetic nervous system, the system responsible for getting you calm and relaxed.
One study linked below indicated that a moderate magnesium deficiency (similar to which commonly occurs in humans) could enhance inflammatory or oxidative stress in the body. Elevated levels of oxidative stress can lead to sleep disruption. Additionally, when these levels are high, it is difficult for the body to restore itself at the cellular level.
Another study showed that based on food diaries, 58% of the participants who consumed less than the U.S. Estimated Average Requirement for magnesium (this varies based on age and gender), had higher levels of C-reactive protein in the blood. Higher levels of C-reactive protein indicate that there is stress or inflammation somewhere in the body.
It is always important to begin by looking at your diet. Consuming foods rich in magnesium like leafy greens, nuts, beans, seeds and whole grains can help your body get the magnesium it needs. Additionally, consumption of excessive amounts of fat, calcium, phosphates, fiber, coffee, and strong tea has been shown to reduce the absorption of magnesium ions in the human body.
If you are getting enough magnesium in your diet but your sleep is still interrupted, you may need to look at other factors that could be impacting your sleep negatively. Limiting caffeine and blue light before bed and avoiding heavy, rich foods are both good places to start.
Sometimes MTHFR variances make it hard for your body to use the magnesium you are putting into it (due to impaired methylation pathways), and supplementation may be necessary. Taking a highly bioavailable version of magnesium, like this one, may prove to be a useful instrument in managing disordered sleep. Always speak with your doctor to ensure you are doing the right thing for your body.
Magnesium has been ubiquitously referred to as the miracle mineral. A quick search on google yields results such as, “Get back on task naturally, “ and “Energy support like no other.” So what’s all the hype really about?
The human body needs adequate levels of magnesium to function properly. It is an essential mineral that promotes mitochondrial health (energy!), glucose metabolism, bone health, intestinal function, and more. Magnesium is a core component of the Earth’s crust and the fourth most abundant mineral in the human body. Additionally, this “miracle” mineral is essential for supporting more than three hundred enzymatic reactions at the cellular level.
The answer is twofold. First, you need to be consuming a diet that is rich in whole, nutrient-dense foods and low in refined carbohydrates and processed sugars. There are various foods that contain high levels of magnesium. Here is a list of some foods, in order of concentration:
Here’s the bad news. Unfortunately, as our food and agricultural system has undergone some change for the worse, minerals like magnesium have been depleted from our soil. A study on cattle conducted over a span of eleven years (2002-2013) showed that over five hundred animals had a mineral deficiency.
Soil that is higher in organic matter and clay does a good job of retaining minerals (like magnesium) and passing those minerals through to the plants. Unfortunately, the soil is not the same as it used to be when our great-grandparents were growing up.
To make things harder, our grocery stores are now stocked with packaged, processed food in addition to highly-sprayed, genetically modified produce. Things like soil depletion, use of chemical-laden fertilizer, and processing of foods have made it harder for plants to retain their nutrients. Critical minerals are being stripped from the soil on a daily basis, which means that even foods that are known to have higher levels of magnesium may not always contain levels that are bioavailable to us.
Other risk factors for magnesium deficiency may vary, but some can include:
The health benefits of probiotics are well-known. Probiotics are healthy bacteria that can help you to improve gut health, lose weight, boost your immune system and enjoy other incredible benefits. Unfortunately, many people who have added probiotic-enriched foods to their diet have been less than impressed by their lackluster results. Before you give up on probiotics and let their potential health benefits escape your grasp, a closer look at how probiotics work and what you can do to boost results is in order.
While many people associate bacteria with illness or contamination, the reality is that there are both good and bad strains of bacteria. Good bacteria are essential for a healthy gut. One of the important roles that they play in your gut is to facilitate the movement of food through your system. This may be particularly important if you suffer from irritable bowel syndrome, inflammatory bowel disease or other digestive conditions. Because a sluggish gut is a common issue in pregnancy, some women benefit from taking a probiotic-enriched supplement containing methylfolate during pregnancy.
There are several strains of healthy bacteria that your body needs for optimal health. Some of these are lactobacillus, bifidobacterium and saccharomyces boulardii. These and other probiotics that are found in supplements and in various foods naturally work in different ways. Because of this, many probiotic supplements contain several different types of healthy bacteria.
Also Read: Folic Acid In Anxiety And Depression
While some people incorporate probiotics into their diet to take their health to the next level, others do so in order to find relief from bothersome and painful health conditions. If your probiotic supplement is not living up to your expectations, you may feel disappointed and frustrated. The dismal results that your current supplement is producing for you may be related to the product that you are taking rather than to your body’s response to probiotics.
Consider that many probiotic supplements and products on the market today only have three strains of bacteria. Because each strain functions in different ways to improve your health, finding a supplement that has a wider range of bacillus strains is a great starting point. Keep in mind that many lactic acid-based probiotics are relatively weak. This is because the manufacturers do not take special precautions to protect the bacteria from the effects of exposure to light, heat, stomach acid and oxygen. Finally, the concentrate of probiotics in the supplement can vary as well. Some products have substantially more spore-based probiotics per capsule or serving than others.
Whether you are taking a probiotic with methylfolate during pregnancy or you want to enjoy the benefits of healthy probiotics for other reasons, you must take the time to identify the best supplement or product on the market. Look for a highly-concentrated supplement that has up to five unique bacillus strains. In addition, focus on the manufacturing process to ensure that the probiotic supplement that you take has superior strength. While it can take time to research the options and to find the best probiotics available, rest assured that your gut will thank you for the effort.
Also Read: Homocysteine and MTHFR weight problems
There’s something about a yummy vitamin that makes you wonder, “Is this really legit?” Because truly healthy, scientifically tested supplements and medications should be capsules or horse pills you swallow with water. Vitamins that taste decent are loaded with sugar and fillers. Only children’s medicines should be flavored because adults should be willing and able to swallow something even if it tastes horrible or doesn’t taste at all.
Not necessarily...but there is an amount of truth to all of that about the flavoring. Gummy vitamins, which have seen a huge increase in popularity over the last several years, do, according to Zhaoping Li, a professor of medicine and chief of the Division of Clinical Nutrition at the University of California, Los Angeles, contain gelatin and“...often have other things in it — glucose or glucose syrup. They often have to add food coloring. And citric acid to keep it stable.”
And, in many cases, vitamin supplements that do have flavorings added simply list them as “natural flavors.” If that seems like a vague label, it’s because it is.
Healthline says that, according to the US FDA's Code of Federal Regulations, natural flavors are created from substances extracted from these plant or animal sources:
Now, if they’re doing things right, a vitamin producer will note on the label if a product may contain shellfish, dairy, or eggs, because of allergies. But even without allergy issues, it’s nice to know exactly where your flavorings come from. Just one natural flavor can contain 50 to 100 ingredients and yet it's still described as "natural blueberry flavor.” To be fair, that doesn’t mean anyone is intentionally keeping you in the dark regarding the ingredients; most vitamin supplements already struggle with fitting all of the required information on the label, let alone adding 50 more ingredients. Even the eyes of the most conscientious consumer would glaze over.
Not always, because not everything that occurs naturally is meant to be ingested. Ora Organic concisely describes flavor being classified as "natural" or "artificial" as a qualification of source alone.
In the end, some artificial flavors and natural flavors have remarkably similar (possibly even the exact same) chemical structure. All this to say if you’re going to use a flavored vitamin supplement, aside from allergens and “Generally Recognized As Safe” status with Food and Drug Administration (FDA), there may not be a need to split hairs.
That should make it easier for nearly 40% of people- who have a hard time swallowing pills. If you can’t swallow pills, but you’re also typically advised not to crush them or split a capsule, flavored vitamins are the way to go. If it’s between that or simply not taking your supplement, it’s an easy decision. Allow your vitamins to taste good.
If you’re looking for high quality, potent, absorbable supplement that also tastes good and isn’t loaded with sugars, there really are options. We make the best product we can with the ingredients you need for your health, but we can’t be experts at everything. That’s why we use flavors made by companies that are FEMA GRAS approved--Flavor and Extract Manufacturers Association of the United States (yes, there’s an association for that) Generally Recognized As Safe. Ingredients are minimal, tastes are great, and we trust their quality.
Most people, it seems, experience a certain amount of what we regularly refer to as the “blahs” during the winter. Winter months in places where winter temperatures really do happen are a veritable breeding ground for low mood.
We leave work and it’s dark by the time we make the commute home, if not when we walk out the door of the office. Gray skies and tree branches--despite the popularity of blue-gray color schemes indoors, it just doesn’t work as well outside. Cold temperatures force us indoors when we might otherwise be frolicking in the sunshine. True blue skies, rich green leaves and grasses, the rainbow of colors in the outdoors and the outfits, fresh air...we miss them when they’re gone.
Add to that the stress of the to-do lists and abundance of company around the holidays, or, in some cases, the lack of company or grieving loved ones. Then throw in the excess of comfort foods, which are really only comforting in the moment, but don’t do our bodies a lick of good in the aftermath.
It’s the perfect storm for irritability, anxiety, sadness, and, for some people, the deeper, harder-to-shake Seasonal Affective Disorder (aptly acronymed SAD).
Rush University Medical Center in northern Illinois (well-versed in surviving long winters) describes the difference.
Winter blues
The most common symptoms are general sadness and a lack of energy. Other symptoms of the winter blues include the following:
SAD
It gets serious, and when it happens every year, as it very well may if SAD is what you’re dealing with, it can become dangerous.
Sunshine is more than just a visual happy maker and a warming tool. When your skin is exposed to sunlight, it makes vitamin D from cholesterol. The sun's ultraviolet B (UVB) rays hit cholesterol in the skin cells, providing the energy for vitamin D synthesis to occur.
Exposure to less natural light and, hence, vitamin D can really cause problems, like
Treating SAD
Toxic, environmental or body burden is defined as the total amount of naturally-occurring and man-made chemicals that are negatively present in the human body. It’s a fluid thing, because there are times when you’re taking in more or fewer toxic elements, and there are times when you’re body is doing a better or worse job of getting rid of them.
Obviously, “toxic” means bad. But what really happens when toxic burden is too heavy?
Functional health expert Dr. Jill Carnahan points out that we only tend to consider and understand toxicity when it causes sudden and definitive symptoms, or when you’ve actually seen someone ingest a substance known to be toxic. But that’s not the most common way people are damaged by toxins. Most exposure is chronic, involves a multitude of toxins, and causes an overload over years.
That overload can lead to (not an exhaustive list; just the most common issues):
And if left unchecked, these more threatening conditions can arise:
No. Exposure to toxins and accumulated toxic burden isn’t good for anyone. But people with MTHFR genetic mutations are especially susceptible to complications, because your body’s methylation process is suffering and you don’t produce the amount of antioxidants, especially glutathione, needed to rid your body of toxins.
This is, again, not an exhaustive list, but is a good starter list for substances, both ones we’re exposed to externally and internally, that add to the body’s toxic burden:
Not quite. Fortunately, there are ways to live a totally normal life AND avoid toxic overload.
Other effective ways to reduce toxic burden: