Health & Fitness

Atom-scale models of proteins that incorporate ligands, like drug molecules, shows a strong correlation between minimally frustrated binding sites and drug specificity. Such models could lead to better-designed drugs with fewer side effects.

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Special activity trackers can be used to fairly accurately determine the respiratory rate of people while they sleep. In the future, activity trackers could be used to detect the early stages of a disease, as a person's respiratory rate can indicate signs of an undetected medical problem.

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Researchers have identified the brain activity for the first time in a newborn baby when they are learning an association between different types of sensory experiences. Using advanced MRI scanning techniques and robotics, the researchers found that a baby's brain activity can be changed through these associations, shedding new light on the possibility of rehabilitating babies with injured brains and promoting the development of life-long skills such as speech, language and movement.

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Researchers have designed a new Optically Pumped Magnetometer (OPM) sensor for magnetoencephalography (MEG). The sensor is smaller and more robust in detecting magnetic brain signals and distinguishing them from background noise than existing sensors. Benchmarking tests showed good performance in environmental conditions where other sensors do not work, and it is able to detect brain signals against background magnetic noise, raising the possibility of MEG testing outside a specialised unit.

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Melatonin is a hormone synthesized in your pineal gland and many other organs.¹ While it is most well-known as a natural sleep regulator, it also has many other important functions.² For example, melatonin:

Is a potent antioxidant3 with the rare ability to enter your mitochondria,4 where it helps “prevent mitochondrial impairment, energy failure and apoptosis of mitochondria damaged by oxidation.”5 It also helps recharge glutathione,6 and glutathione deficiency has been linked to COVID-19 severity

Plays an important role in cancer prevention7

Is important for brain, cardiovascular and gastrointestinal health8

Boosts immune function in a variety of ways

May improve the treatment of certain bacterial diseases, including tuberculosis9

Helps quell inflammation

May prevent or improve autoimmune diseases, including Type 1 diabetes10

Is an important energy hormone that can influence your energy level11

Helps regulate gene expression via a series of enzymes12

Has anticonvulsant and antiexcitotoxic properties13

Melatonin Also Has Important Role in COVID-19 Treatment

Melatonin has also been shown to play a role in viral infections¹⁴ and according to a June 2020 research paper^15,16,17 in Life Sciences journal, it may be an important adjunct to COVID-19 treatment. According to the authors, melatonin attenuates several pathological features of COVID-19, including:¹⁸

• Excessive oxidative stress and inflammation
• Exaggerated immune response resulting in a cytokine storm
• Acute lung injury
• Acute respiratory distress syndrome

They point out that melatonin is also “effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes.”¹⁹

The scientific review paper,²⁰ “Melatonin Potentials Against Viral Infections Including COVID-19: Current Evidence and New Findings,” published October 2020 in Virus Research journal, also summarizes the many potential mechanisms by which melatonin can protect against and ameliorate viral infections.

The authors review research looking at melatonin’s beneficial effects against a variety of viruses, including respiratory syncytial virus, Venezuelan equine encephalitis virus, viral hepatitis, viral myocarditis, Ebola, West Nile virus and dengue virus. Based on these collective findings, they believe melatonin may offer similar protection against SARS-CoV-2.

Melatonin Reduces Risk of Positive COVID-19 Test

Data^21,22 from Cleveland Clinic also supports the use of melatonin. Here, the researchers analyzed patient data from the Cleveland Clinic’s COVID-19 registry using an artificial intelligence platform designed to identify drugs that may be repurposed.^23,24

By identifying clinical manifestations and pathologies shared by COVID-19 and 64 other diseases, they were able to conclude that certain proteins associated with chronic diseases are highly connected with SARS-CoV-2 proteins. Put another way, a number of proteins appear to play a key role in the pathologies seen both in COVID-19 and other chronic diseases. For example:²⁵

“Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease.

Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2).”

The diagram below illustrates (among other things) the basic pathogenesis of SARS-CoV-2 (figure A) and the network of disease manifestations associated with the infection (figure C).

These connections suggest that drugs already in use for a chronic disease may be repurposed and used in the treatment of COVID-19, as it acts on one or more shared biological targets. Melatonin stood out in this regard. Patients who used melatonin as a supplement had, on average, a 28% lower risk of testing positive for SARS-CoV-2. Blacks who used melatonin were 52% less likely to test positive for the virus.

Confounding variables adjusted for in the calculations included age, sex, race, smoking history and several known comorbidities. The authors point out that while the findings look promising, large observational studies and randomized controlled trials are still needed to validate the clinical benefits of melatonin.

Two key data points missing from the analysis are the dosage used and the length of supplementation. These data were not included in the patient registry, so we don’t know how much melatonin is required to lower your risk of SARS-CoV-2 infection to the degree found in this study.

High-Dose Melatonin Successfully Treats COVID-19

It’s possible that higher doses than those used for sleep may be needed, at least when treating an active infection. A recent case series²⁶ published in the journal Melatonin Research details how high-dose intravenous melatonin can benefit patients with COVID-19 pneumonia.

Here, patients were given 36 mg to 72 mg per day in four divided doses as an adjunct therapy to standard of care. Most supplements contain between 0.5 mg and 5 mg, and when used for sleep, you’d typically start with the lowest dose and work your way up as needed.

All of the patients given melatonin improved within four to five days, and all survived. On average, those given melatonin were discharged from the hospital after 7.3 days, compared to 13 days for those who did not get melatonin. This is far better than the expensive treatment Remdesivir, which costs over $3,000 and doesn’t produce anywhere near this improvement.

Other Doctors Are Also Using Melatonin Against COVID-19

Dr. Richard Neel and colleagues at Little Alsace and Uvalde Urgent Care clinics in Texas also report using high-dose melatonin in combination with vitamin C and vitamin D, and had as of the last week of July 2020 successfully treated more than 400 patients.²⁷

As reviewed in a section below, melatonin enhances vitamin D signaling and the two work synergistically to enhance your mitochondrial function. Melatonin and vitamin C are both also involved with ACE2, the receptor that SARS-CoV-2 uses to gain entry into the cell.

Together, melatonin and vitamin C help reduce SARS-CoV-2 virulence by inhibiting NLRP3 inflammasomes, which in turn inhibits cytokine storms. The Front Line COVID-19 Critical Care Working Group (FLCCC)²⁸ also lists melatonin as an optional addition to their MATH+ protocol for COVID-19.

How Melatonin Combats COVID-19

Research suggests melatonin may have the ability to combat COVID-19 via several different mechanisms. For example, it’s been shown to regulate immune responses and prevent cytokine storms.²⁹ As explained by the authors of one such study,³⁰ when your immune cells are in a hyper-inflammatory state, their metabolism changes in a way similar to that of cancer cells:

“Similar to cancer cells … immune cells such as macrophages/monocytes under inflammatory conditions abandon mitochondrial oxidative phosphorylation for ATP production in favor of cytosolic aerobic glycolysis (also known as the Warburg effect) …

The change to aerobic glycolysis allows immune cells to become highly phagocytic, accelerate ATP production, intensify their oxidative burst and to provide the abundant metabolic precursors required for enhanced cellular proliferation and increased synthesis and release of cytokines ...

Because of melatonin's potent antioxidant and anti-inflammatory activities, it would normally reduce the highly proinflammatory cytokine storm and neutralize the generated free radicals thereby preserving cellular integrity and preventing lung damage.”

Cytokine storm is one of the reasons why sepsis (blood poisoning) is so lethal, and studies have confirmed melatonin has a favorable influence on sepsis. (Sepsis is also a feature of severe COVID-19.) As reported in a 2010 study in the Journal of Critical Care:³¹

“Melatonin is an effective anti-inflammatory agent … Its anti-inflammatory action has been attributed to inhibition of nitric oxide synthase with consequent reduction of peroxynitrite formation, to the stimulation of various antioxidant enzymes thus contributing to enhance the antioxidant defense, and to protective effects on mitochondrial function and in preventing apoptosis.

In a number of animal models of septic shock, as well as in patients with septic disease, melatonin reportedly exerts beneficial effects to arrest cellular damage and multiorgan failure …

Apart from action on the local sites of inflammation, melatonin also exerts its beneficial actions through a multifactorial pathway including its effects as immunomodulatory, antioxidant and antiapoptotic agent.”

More recently, a 2019 animal study³² in the journal Frontiers in Immunology discusses how melatonin can protect against polymicrobial sepsis — i.e., sepsis caused by more than one microbial organism — which has a twofold higher lethality than unimicrobial sepsis (sepsis caused by a single microbe).³³

In this case, melatonin appears to offer protection by having an antibacterial effect on white blood cells called neutrophils. A high neutrophil count is an indicator for infection. Melatonin may also combat SARS-CoV-2 infection by:³⁴

Suppressing oxidative stress35

Regulating blood pressure (a risk factor for severe COVID-19)

Improving metabolic defects associated with diabetes and insulin resistance (risk factors for severe COVID-19) via inhibition of the renin-angiotensin system (RAS)

Protecting mesenchymal stem cells (MSCs, which have been shown to ameliorate severe SARS-CoV-2 infection) against injuries and improving their biological activities

Promoting both cell-mediated and humoral immunity

Promoting synthesis of progenitor cells for macrophages and granulocytes, natural killer (NK) cells and T-helper cells, specifically CD4+ cells

Inhibiting NLRP3 inflammasomes36

General Guidance for Supplementation

As mentioned, it’s very difficult to make dosage recommendations based on the limited evidence currently at hand, but since Cleveland Clinic looked at the supplements patients reported using, it seems reasonable to assume they were using it as you typically would. Most melatonin supplements contain between 0.5 mg and 5 mg.

In the case report mentioned earlier, patients were given 36 mg to 72 mg of melatonin intravenously per day, which would likely be excessive for prophylactic use. That said, research³⁷ has found no adverse effects for dosages ranging from 20 mg up to 100 mg.

Whatever dose you take, and I recommend starting low, at 1 mg or less, be sure to take melatonin at night, before bed. Rising melatonin levels is the reason you feel sleepy in the evening, so it’s ill advised to take it in the morning or during the day, when your natural level is (and should be) low. If you happen to wake up in the middle of the night, especially if you’re exposed to a light source, you could also take some then, to help you go back to sleep.

Melatonin is also best taken sublingually, either in the form of a spray or sublingual tablet. Sublingually, it can enter your blood stream directly and doesn’t have to go through the digestive tract. As a result, its effect will be felt more rapidly.

Melatonin and Vitamin D Are a Winning Combo

Another supplement of crucial importance in the age of COVID-19 is vitamin D. Interestingly, melatonin enhances vitamin D signaling, and optimizing your vitamin D may be one of the most beneficial steps you can take to lower all of the risks associated with COVID-19, from reducing your risk of testing positive to lowering your risk of severe infection and death.

To learn more about this, download my free vitamin D report from StopCovidCold.com. Together, melatonin and vitamin D synergistically act to optimize your mitochondrial function. In fact, your mitochondria are the final common target for both.³⁸

A deficiency in either vitamin D or melatonin has been associated with the pathogenesis of several chronic diseases, including high blood pressure, cardiovascular disease, metabolic syndrome and diabetes, just to name a few.³⁹

These conditions have also emerged as comorbidities that significantly raise your risk of death from COVID-19. Synthesis of both vitamin D and melatonin is also dramatically reduced with advancing age, and old age is a primary risk factor for COVID-19 death. So, while vitamin D3 and melatonin supplementation may be beneficial for most people, it’s particularly important for the elderly.

Support Your Body’s Production of Melatonin and Vitamin D

Keep in mind, however, that it makes little sense to take a supplement unless you’re also seeking to optimize your body’s natural production. In the case of melatonin, this includes making sure you get good sleep on a regular basis.

You also need a good dose of natural sunlight around midday to synchronize your circadian clock so that your body produces melatonin at the appropriate time (i.e., in late evening). As the evening wears on and the sun sets, you’ll want to avoid bright and all blue lighting, as blue light inhibits melatonin synthesis. Blue lighting is predominant in LED and fluorescent bulbs that are “cool white.”

Sun exposure, of course, is also the ideal way to optimize your vitamin D. I recommend getting sensible sun exposure on large portions of your body on a regular basis, ideally daily. For further guidance, see “The Risks and Benefits of Sun Exposure.”

If for whatever reason you cannot get sufficient amounts of sun exposure, consider taking a vitamin D3 supplement (along with a little extra vitamin K2 to maintain a healthy ratio between these two nutrients).

I personally have not taken any oral vitamin D for well over 10 years and my levels are typically over 60 ng/mL, even in the winter. I have, however, started taking sublingual melatonin a few years ago as I am now in my mid-60s, even though I sleep in pitch dark and get bright sun exposure during the day.

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From the time you were a small child, you may have been conditioned to expect new and exciting things as autumn arrives. Every fall, children go back to school, see their friends and begin to anticipate the holiday season. One of the fruits closely associated with fall is pumpkin.

From pumpkin pie to pumpkin spice lattes or jack-o-lanterns it’s likely you associate fall with some type of pumpkin. Kathryn Lively, professor of sociology at Dartmouth College, spoke with a reporter from The Huffington Post about the expectations children have and how this conditions a response pattern that often travels into adulthood.¹

Fall is a structural landmark, in the way significant dates help create structure in the perception of the passage of time.² For example, just as January 1 is a landmark associated with developing personal growth and development goals, fall may be a time when your anticipation begins to grow, and you’re motivated to learn new skills or change behaviors.

Licensed psychologist and professor at Chapman University Amy Jane Griffiths, Ph.D., says, “We all crave the comfort and security that comes with traditions and predictability.”³ Many of us have traditions and events associated with fall weather, while others may dread the leaves changing or signs that winter is coming.

What Color Are Your Pumpkins?

Many have an interest in the science behind your anticipation of fall weather, fall foods and the hope of curling up with a blanket and a good movie. But it may still be difficult to explain the vast number of people who buy pumpkins each fall. In the U.S., Illinois is the No. 1 producer of this round orange squash, growing twice as many each year than in the other five top producing states.⁴

While you might think of it as a vegetable, the pumpkin is a fruit that's known as much for its place in the kitchen as on your front porch. Mary Liz Wright, a University of Illinois Extension specialist, does not advise using your typical jack-o-lantern pumpkin in your fall recipes.⁵

This is because there are two distinct species of pumpkin. The first has been bred for size, structure and color to enhance your fall decor. The second is bred for consistency, flavor and texture of the meat. Pumpkins that are bred for flavor are tan or buckskin color on the outside with bright orange flesh on the inside.

They're also more reminiscent of butternut squash in shape, rather than the more rounded outline of decorative pumpkins. Nathan Johanning, also a University of Illinois Extension specialist, spoke about the 2020 fall crop and the agritourism trade pumpkins support, sharing that one farm in Illinois had 5,000 tourists pass through in one weekend.

If you're planning on saving the flesh from your pumpkins, Wright advises you cook and freeze it, since it is not advisable to can pumpkin or even pressure can it. The center of the dense flesh may not get hot enough to prevent botulism growth, which you can avoid by cooking it first and then freezing it.

Nutritious and Delicious Pumpkins

There are many health benefits to eating pumpkin and pumpkin seeds, as you'll see in this short video. Although you can buy them year-round at the store, consider adding pumpkins to your garden since nearly every part of the plant can be eaten. You'll be assured of a toxin-free fruit from which you can harvest the seeds as well as carve and cook your pumpkins in the fall.

Dried pumpkin seeds, also called pepitas, are high in healthy fats and rich in omega-3 fats, zinc, calcium, iron and an array of phytochemicals.⁶ After being dried and shelled, the seeds have just 180 calories in one-fourth cup and are also packed with manganese, phosphorus, copper and magnesium.⁷

People have used pumpkin seed extract and oil in the treatment of benign prostatic hyperplasia. This is a noncancerous enlargement of the prostate gland that may respond to the nutrients found in pumpkin seeds. Because most of the studies have involved extracts or oils from pumpkin seeds, it's not possible to extrapolate the information to eating the pumpkin seeds themselves.⁸

The meat of the pumpkin contains only 49 calories in 1 cup of cooked mashed flesh. It is rich in riboflavin and vitamins A, C and E.⁹ The rich orange color indicates the high level of beta-carotenes and antioxidants that your body uses to neutralize free radicals.

The high levels of vitamin A and C have a positive impact on your immune system, and it is a major source of lutein and zeaxanthin linked to healthy eyesight.¹⁰ The high levels of potassium, vitamin C and fiber are all associated with cardiovascular benefits.

For instance, one literature analysis found an inverse association between potassium and the risk of stroke.¹¹ Another study demonstrated people with higher levels of potassium intake had lower risk of high blood pressure.¹² The levels of beta-carotene, vitamin A and vitamin C all contribute to healthy skin, collagen production¹³ and protection against the damage of ultraviolet rays.¹⁴

Pumpkin Seeds May Reduce Your Risk of Kidney Stones

In addition to the health benefits listed above, pumpkin seeds have a special superpower: They protect your kidneys by reducing the risk of calcium-oxalate crystal formation, better known as kidney stones. There are four types of kidney stones that can form, including calcium, struvite, uric acid and cystine stones.¹⁵ Of these, calcium oxalate is the most common.

Nearly 80% of calcium stones that form are calcium oxalate. By manipulating urine chemistry through dietary intake, you can help prevent calcium stone formation. The highest urine chemistry risk factors for calcium oxalate crystals are hypercalciuria and hyperoxaluria.¹⁶

Dietary risk factors that increase your potential for calcium oxalate stones include chronic dehydration and a diet that is rich in protein, oxalates, sodium and sugar.¹⁷ People with certain digestive disorders, such as inflammatory bowel disease, can also have a higher risk of calcium oxalate kidney stones. Oxalate can be found in these foods:^18,19

Beans	Beets	Beer
Chocolate	Coffee	Cranberries
Peanuts	Rhubarb	Soda
Sweet potatoes	Tea (black)	Dark green vegetables, such as spinach

One study evaluated the ability of pumpkin seed supplementation to change the chemistry of the participants’ urine and reduce the risk of calcium oxalate crystal formation.²⁰ Researchers engaged 20 boys from the Ubol Province in Thailand where there is a high incidence of kidney stones.²¹ 

During the experiment the boy’s urine was measured before any intervention as a control period. During two periods of the intervention they received an oxalate supplement and a pumpkin seed or orthophosphate supplement. The participants’ urine chemistry was tested before and after each intervention.

The results of the study showed that while the boys were receiving the pumpkin seed supplement, the urine chemistry had the lowest potential risk for calcium oxalate crystal formation. The researchers found the high levels of phosphorus in the pumpkin seed may be a "potential agent in lowering the risk of bladder-stone disease."²² 

Pumpkin Spice Blend Elicits an Emotional Response

The scents associated with pumpkin pie are not strictly from pumpkin but, rather, a combination of cinnamon, nutmeg and clove, which are the traditional spices used in the pie. This combination of scents can trigger a strong emotional response in your brain, which causes you to recall experiences associated with the smell.²³

The emotional response that odors generate have an impact on your decision to like or dislike something. Your sense of smell and memory are closely linked since scents travel from the limbic system through the amygdala and hippocampus, which are regions of the brain related to emotion and memory.²⁴

The scent of pumpkin spices is popular during the fall months, especially in homemade products and the Starbucks Pumpkin Spice Latte. Catherine Franssen, Ph.D., director of psychology at Longwood University, is a fan of the flavor and understands why this particular combination of spices elicits an emotional response. She commented to CNN:²⁵

"Since these are popular spice combinations, it's very likely we would have encountered some or all of them combined in a favorite baked good in a comforting situation, like a family gathering, early in life. It's not just the pumpkin spice combo but that we've already wired a subset of those spices as 'good' very early in life."

Starbucks seemed to stumble onto their popular Pumpkin Spice Latte in 2003 when it was first released.²⁶ Each fall the Pumpkin Spice Latte drink makes a return to stores, along with other “pumpkin-flavored” drinks — which may or may not actually have pumpkin in them — and baked goods. This year it’s the Pumpkin Cream Cold Brew.²⁷

In a press release, Peter Dukes, product manager who led the development of the Pumpkin Spice Latte, commented, "Nobody knew back then what it would grow to be. It's taken on a life of its own."²⁸

However, as enticing as the scent may be, the product is loaded with sugar and packs a whopping 52 grams of carbohydrates into a 16-ounce mug.²⁹ Instead, consider making the healthy and tasty alternative at home demonstrated in the video below.

Neuroscience, Sugar Addiction and Marketing

The emotional response generated by scent is something marketers take advantage of. Pleasant scents affect your mood, which is a way of engaging your hand-to-wallet response.

In experiments comparing odorless placebo sprays against fragrances, researchers found while you will have a response to the placebo when you anticipate the fragrance, the actual scent has a dramatic effect on improving your mood.³⁰

Although your preference is highly personalized, a general assumption is made that most people will find pumpkin spice in the fall and cinnamon during Christmas associated with good memories. As the scent of pumpkin spice triggers a happy memory, it can also trigger a desire to buy a cup. Franssen comments on the neuroscience involved in scent and advertising:³¹

"When an odor or flavor — and 80 percent of flavor is actually smell — is combined with sucrose or sugar consumption in a hungry person, the person learns at a subconscious, physiological level to associate that flavor with all the wonderful parts of food digestion.

[For that reason] the pumpkin spice latte is actually, scientifically, kind of addictive. Not quite the same neural mechanisms as drugs of abuse, but certainly the more you consume, the more you reinforce the behavior and want to consume more."

The popular trend of promoting all things pumpkin in the fall even generated a hoax in 2014 when a Facebook meme reported Charmin toilet tissue would soon be released in a new pumpkin spice scent. Not soon after Charmin Company tweeted: "While we love it, we can promise you this. You will not be seeing #PumpkinSpice Charmin anytime soon. #StopTheMadness"³²

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