Robert True

Coronavirus: Information to Help You

We have new information from the Chinese data and other resources on the behavior of the virus, and options fro protection from the corona virus that will help us understand the disease better and how to handle it. After the huge epidemic that started in Wuhan, China, the thousands of people who contracted the virus and the deaths of so many of their population, the Chinese now understand the behavior of the Covid 19 virus better than anywhere in the world. We can thank them for doing autopsies on those who died and had the virus and the results that these pathology evaluations have provided. The Italian experience has also given us great incite into this viral pandemic.

Of those who contract the disease, if all goes well with appropriate medical care and good health, around 98% of patients survive the disease, but around 2% suffer such severe respiratory problems that they die, unable to recover from the disease primarily due to the lung problems the disease causes. If they survive the acute episode, lung problems tend to be worse by days 10 to 13 of the illness, and resolution of the radiological signs and the symptoms by after 14 days.[1a

Thus, there is HOPE. Even if you get the virus, there’s a good chance that you will survive, assuming you are healthy and do protective actions that improve your chances. We will discuss many of the actions that you can do to help you survive the coronavirus infection.

Symptoms of Coronavirus

Due to the prominent lung involvement, the most common symptoms following infection by the virus that will give you a clue that you might be getting the viral illness are fever, cough, and shortness of breath. Other symptoms of the virus include sore throat, chills, diarrhea, vomiting, muscle aches, malaise, abdominal pain, and a severe headache.

If you just have a scratchy throat and no fever, or you feel a little achy, most likely you don’t have the corona virus and it could be something else, such as a cold, flu, allergies, etc. For those who have been prescribed the Coronavirus combo protocol of hydroxychloroquine[2] and azithromycin, you should depend more on the more common symptoms listed above before you start taking the meds.

Of note, there are few interactions of the use of these two medications. One rare interaction problem could be development of arrhythmias in around 0.35%[3] of those who took this combo. Since the incidence of death from coronavirus is up to 4%, the risk: benefit ratio favors use of the two meds. In other words, it most likely won’t hurt you, but could benefit you markedly.

Lung Changes from Coronavirus Infection

The viral illness, when symptomatic, is characterized by obstruction of the lung pathways (the bronchi) with thick mucous that thickens and may obstruct the airways. With obstructed airways, you get poor ability to breath in oxygen and exhale carbon dioxide, and when severe results in asphyxiation with subsequent cardiac failure and death in those 2%-4% who progress.

In order to treat these lung problems, one must open the airways to give medications that could help this problem. However, this may take a few days, and may require support in the ICU with respirators. Acute respiratory distress syndrome (ARDS) may occur,[1] which is a very severe pulmonary condition with a very high death rate, resulting in worsening inflammation to the lungs and a poorer prognosis.[4]

What You Can Do if You Get the Corona Virus

The Chinese experience has suggested that there are potentially 10 modifiable actions that you can do to help you fight the infection. These have not been verified as being effective, but the Chinese feel these actions work. They are relatively safe things you can do, so it’s advisable to do them, whether you are trying to prevent the disease or you see signs of the viral illness.

  1. Drink lots of hot liquids: These can include beverages such as coffee, teas, hot soups, warm water, etc. Consider taking sips of these every 20 minutes if you have symptoms of the disease. Doing so may regularly wash any virus particles that may be in your mouth down into your stomach where the acid in the stomach gastric juices can neutralize (kill) the virus. Transmission of the virus through the mouth is probably the most common route.
  2. Gargle with an antiseptic in warm water. Consider using a mixture of half a lemon, ½ to 1 teaspoon of vinegar or salt in a glass of warm water.
  3. Wash your hands regular, and thoroughly, especially after touching surfaces that may have been contaminated with the virus. As a general rule, that could be anybody’s hands, mouth, or even inanimate surfaces. Wash with any soap that produces a foam, and wash for 20 seconds.
  4. Shower with soap and hot/warm water every day. Every morning is fine, but ideally, when you get home after being on the street or outside your house, you should avoid sitting down anywhere and go straight to take a shower immediately after you get home with lots of soap and water.
  5. Wash your clothes daily. If you cannot wash your clothes daily, hang them in direct sunlight which also neutralizes the virus.
  6. Wash all surfaces regularly, especially metallic surfaces. The virus may remain viable on metallic surfaces for up to 9 days. If you touch these in a public area, wash your hands with soap and water and don’t touch you face, especially your eyes, nose and mouth. Regularly clean handles, rails and door handles in your house. Note that anti-bacterial solutions will not work. This is not a bacterium; it is a virus. You must use a dilute solution of Clorox. In 1 liter of water (around one quart), add 10 cc (around 1/3rd ounce or 2 teaspoonfuls) of bleach (5.25% sodium hypochlorite), or a 1:100 bleach:water solution.[5] Use a sprayer bottle and let it sit for a few minutes before you wipe it off.
  7. Don’t smoke! This really decreases your immune system and ruins your lungs making it easier for the virus to produce its nasty and deadly effects on your lungs. Smoking is a death wish, not only for this virus, but for other causes of death.
  8. Eat plenty of vegetables and some fruit. These have many immune-boosting ingredients that improve your bodies’ ability to fight off infections. Mix them, and do lots of colors, not just green, but red, yellow, and purple.
  9. Avoid getting the flu or a bad cold. This increases your risks of lung inflammation before you even get the virus. How do you avoid these? We recommend you decrease any type of severe temperature shifts or other stress on your body. When temperatures go down (or up) rapidly, this can reduce your resistance. The viruses that you’ve already been exposed to may be in your body already, but you don’t have symptoms because your good immune system fights them back. However, when your resistance is low, i.e. your immune system is shocked from the stresses and its efficiency is not so good, these viruses lurking within you tend to multiply rapidly because your weakened immune system can’t fight them off, so you get the colds and viral conditions even though you can’t even remember being exposed to anyone with them. Thus, keep your immune system maxed up by avoiding stresses, including large temperature shifts and other stresses to your body.
  10. If you feel symptoms of viral infections, attack it immediately. If you have a sore throat or raspy throat, use the above methods to reduce the potential viral load into your lungs. The virus can enter your body primarily through your mouth, and it appears to stay in your mouth for 3-4 days before it passes into your lungs. Thus, the warm water sips regularly and the antiseptic gargles are good things to do to avoid you getting a severe case of the coronavirus. Avoid cold drinks, especially cold sugary drinks.

Other Actions You Can Do

We also recommend that you take supplements that are immune boosters. Boosting your immune system to more efficient levels may enable you to fight off the virus better. These supplements include Zinc, vitamin C, curcumin, resveratrol, green tea extract, quercetin, and omega 3 fish oils. These may all boost your immune system. Make sure you maintain high levels of vitamin D, so take around 5,000 u per day. Note that we have all these great quality products at our office at the correct dose if you would like to purchase them from us.

Along with these products are peptides that boost your immunity. These are nature’s natural signaling compounds that tell the cells of your body to be more efficient. In the case of the peptides for the coronavirus, called the Thymosin’s, they activate your immune cells to be more active against invaders to your body, such as viruses, including the corona virus. Read more about these on this blog.

Another option for protection is to prescribe two medications: Hydroxychloroquine (or chloroquine) and azithromycin for around 5 days if you get the symptoms of the viral condition (noted above). Presently, the lab test for the coronavirus takes around 5 days to come back. In the meantime, you may become quite ill. This combination may decrease the severity of the viral illness through multiple pathways and has been shown to work anecdotally. You would essentially start and finish the course of treatment before you would even know if the coronavirus lab test was positive or negative. If you waited for the test, the severity of the illness could become much worse.

We offer office visits and telemedicine visits/consults to discuss these options. There are side effects from these medications that must be discussed before prescribing them and we need to see if you are a candidate for use of them. If you’re interested, call use to book a consultation. Understand that all these options are not approved treatments by the FDA. Per FDA requirements, we must tell you that the statements we use for usage of supplements, or any modalities not approved by the FDA, are not intended to say they prevent, diagnose, treat, or cure any disease.

Social Distancing Concepts

There are a lot of people who are critical of President Trump’s and the CDC’s recommendations of social distancing. Anyone who thinks that this social distancing is not necessary and is creating great havoc in our society obviously does not have a grasp of the situation. This contrary thought is very damaging to the nation and potentially very harmful to others and to those who say this.

The purpose of Social distancing is to prevent the rapid spread of the virus. If there is one thing that we can learn from the Italian and Wuhan experiences of the rapid invasion of the coronavirus throughout their countries it is this: we must prevent the rapid spread of the virus, which will happen (for sure) if we just allow everyday life to occur, people to gather closely, planes to fly to and from where ever, and business with close contacts to occur like always. By limiting all this, it allows the spread of the disease to occur slowly, to slowly utilize and hopefully have enough of the great medical resources available for all of us who need them without overwhelming the system.

None of us have any immunity to this virus and it is very contagious. Most likely almost all of us will get the disease sooner or later. However, if allowed to spread rapidly, we would see thousands of cases of the coronavirus illness rapidly, which will overwhelm our medical system. Anywhere from 10% to 20% of people who contract the virus will require respiratory support and treatment in ICU’s with respirators. There’s not enough of these available if a huge number of people get the viral disease at the same time.

Thus, there would be some people with serious lung complications from the virus (as discussed above) who will be left out and will not have access to these wonderful medical modalities, such as respirators. The consequence of this is that they have more chance of dying. And this is what happened with the Italian situation. Their mortality rates went up to 8%, while most endemic areas with adequate resources and social distancing concepts in place have mortality rates much less, around 2% to 4%.

Bottom-line, President Trump and the CDC are saving the lives of thousands of people in the United States. This is prevention, and we don’t always see the effects of prevention since the ones who would have gotten the severe disease, didn’t, so it’s not too apparent. We have to look at the studies to get the right answers. And the Italian and Wuhan situations are proof that without social distancing the results are much more devastating than with it.

Granted, this social distancing is causing tremendous economic turmoil: people are losing jobs, the stock market is tanking, there may be a terrible global recession. But what if it were your mother or father who didn’t get that respirator or ICU bed? You can see how important this concept it.

You’ll get another job in time, the market will bounce back eventually, the recession will also bounce back eventually. But you won’t get your parents back if they die of the virus, which could be more likely if all of the US didn’t take this very drastic position.

Conclusion

In conclusion, there are many lung changes that occur in people infected with the coronavirus. If extreme, admission to ICU and respirator support are necessary, for severe lung conditions can develop such as ARDS. These can result in death, although the majority of people who contract the virus survive.

There are many actions that you can take to help prevent yourself from getting the coronavirus, and there are protective options that could potentially help you, although not approved by the FDA. The concept of social distancing is perhaps the best action we all can presently do to prevent the overwhelming spread of the virus that would also overwhelm our medical system and result in not having enough facilities for those severely ill, which most likely would subsequently and markedly increase the death rate from the disease.

If you would like to discuss your options more thoroughly and get some of these modalities, call and make an appointment for a consultation. We do offer telemedicine consults to allow for further social distancing to be maintained.

References:

[1] Lai, CC, et al.  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Internat. Journ of Antimicrobial Agents. 55(3), march 2020, 105924. doi.org/10.1016/j.ijantimicag.2020.105924

[1a] Pan, F. et al. Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia. Radiology, Feb 13 2020https://doi.org/10.1148/radiol.2020200370

[2] Specific Antiviral Therapy in the Clinical Management of Acute Respiratory Infection with SARS-CoV-2 (COVID-19). Link

[3] Sbaih N, et al. Potentially Serious Drug Interactions Resulting From the Pretravel Health Encounter, Open Forum Infectious Diseases, Volume 5, Issue 11, November 2018, ofy266, https://doi.org/10.1093/ofid/ofy266

[4] Xu Z, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine.February 18, 2020.  DOI:https://doi.org/10.1016/S2213-2600(20)30076-X

[5] The Use of Bleach. https://www.info.gov.hk/info/sars/en/useofbleach.htm

https://www.ncbi.nlm.nih.gov/books/NBK214356/

Robert True

Coronavirus Protection Actions

No doubt that many of you have been following the news on the novel coronavirus COVID-19 and wondering about the true risk of this virus. The honest answer is that we still don’t know but most experts are expecting that it will have community scale in the US within 8 weeks.  That means it will start to effect travel, work, and schools even more than it already has.  We believe that preparation for this event is essential, as a result, we have prepared some recommendations below.

 

What You Can Do To Be Prepared

1.Face masks, can they help?

 

Most common surgical face masks will not protect you from the Coronavirus. They do let air and small particles, such as viruses pass through, so they act as false protection from the virus.

If you want to wear a mask, you need a more effective one, such as a N95 respirator, which is a respiratory protective device designed to achieve a very close facial fit and very efficient filtration of airborne particles.

The ‘N95’ designation means that when subjected to careful testing, the respirator blocks at least 95 percent of very small (0.3 micron) test particles. If properly fitted, the filtration capabilities of N95 respirators exceed those of face masks. However, even a properly fitted N95 respirator does not completely eliminate the risk of illness or death.

Children and men with beards -forget it! 

N95 respirators are not designed for children or people with facial hair. Because a proper fit cannot be achieved on children and people with facial hair, the N95 respirator may not provide full protection.

Other possible FDA approved respirators are below.

3M™ Particulate Respirator 8670F

3M™ Particulate Respirator 8612F

Pasture Tm F550G Respirator

Pasture Tm A520G Respirator

2. Frequent handwashing. One of the common transmissions of viruses is touching public items then touching your face, eyes and nose, thus transmitting the virus into you. Frequent handwashing with soap and water is highly recommended as a great hygiene action. In particular, don’t touch your eyes, mouth and nose without completely washing your hands, because the mucous membranes of those areas can absorb the virus easily. Transmission through the eye is a common vector for the aerosolized virus.

 

There are no FDA approved drugs available that can prevent the transmission of the Coronavirus or protect you from it. However, there are several off-label non-FDA approved medications that may help. Particularly helpful are peptides, which are chains of amino acids that can signal certain processes to occur within your body, such as boosting your immune system. Each is slightly different in their effects, and there have been studies suggesting good efficacy as anti-viral medications.

3. Consider using peptides to boost your immune system for protection against the Coronavirus.

Peptide Options

A. Thymosin alpha-1 (TA-1) – Thymosin alpha-1 is the most recommend peptide for immune stimulation, i.e. to boost the efficiency of you own immune system to fight off the virus.  This may be used as a preventive or prophylactic method to decrease the chance of you getting the viral illness. Boosting your body’s ability to kill the virus is a great option for potential protection from the virus.  The peptide had been used with other viruses and found to be effective, but this effect has not been confirmed in clinical studies since the coronavirus illness is too recent. The most common dose it at 450mcg daily.

To learn more about TA-1, Click the buttons below to learn more

Immune Modulation with Thymosin Alpha 1 Treatment
C. Selank: Selank is a variant of the immune molecule tufstin and has potent antiviral properties in addition to its neurological effects. It is usually used as a peptide to reduce stress and anxiety. Antiviral characteristics of Selank were evaluated in both in vitro and in vivo against influenza virus strain H3N2 and H5N1 and Herpes virus 1, 2 types. It was shown that Selank may have the prophylactic effect during influenza infection and therapeutic effect during herpes virus infection. It could also be helpful for COVID19. As with Thymosin A4, no studies have confirmed that this therapy is effective, but since it is effective with other similar viruses, it could be useful for the coronavirus.Antiviral Properties of Structural Fragments of the Peptide Selank

Neurotrophic Peptid Called Selank With Antiviral Activity Against Human and Bird Influenza and Herpes Virus Infections

D. Thymosin Beta-4 – Natural killer (NK) cells are essential for defense against tumors and virus-infected cells. These cells are activated in by INF-Gamma. IFN-gamma is activated by IL-18 which TB4 upregulates. Thus, TB4 has been studied for many immune related diseases. Similar to TA1, T4 boosts your immune system to help it fight off viruses, and it is postulated that it would do the same for the coronavirus.Interleukin-18-mediated interferon-gamma secretion is regulated by thymosin beta 4 in human NK cells
If you want to be proactive when it comes to getting the Coronavirus Covid-19, now you have some options. We do suggest that people who travel a lot or are exposed to many other people in public places consider doing one of the peptide options to help protect yourself from the virus. In addition, they have other beneficial effects that may help you in many other ways. Further information on these peptides are on this blog.
Robert True

Alzheimer’s Disease Prevention, Part 2: How do You Prevent it?

In Part 1 of this blog series on Alzheimer’s disease, we discuss how Alzheimer’s disease (AD) is caused by metabolic stresses producing ROS. ROS (reactive oxygen species) are free radicals that result in damage to micro-structures within the brain cells. This damage then results in an immune response by the body to repair the damage and when excessive causes inflammation.

This inflammation causes destruction of the nerves, collapse of their exoskeletons and the formation of inflammatory tangles. A sticky substance called amyloid collects on the nerves, causing further problems. As the destruction progresses, the memory and the mind deteriorate and ultimately result in the frail debilitation and slow death we see in AD patients.

None of us wants this, so our emphasis should therefore be to prevent the problem. Prevention is the best and only medicine for AD that we have currently that really works. There is no cure. So, let’s discuss what you can do to prevent AD from ruining and shortening your life.

Keys to Prevention of AD: Reduce Metabolic Stress

Focus should be on prevention of Alzheimer’s disease. If you can prevent the formation of ROS, perhaps you could help prevent the disease. Preventing ROS is a multifactorial process that must be started early in life. Changes in the brain from AD start 20 to 30 years before the symptoms appear, and no one knows who will be affected.

Thus, you must start at least in your 30’s to 40’s for the best benefit. But starting even earlier is also good to develop the right habits for a healthy lifestyle. Regardless of your age now, start to practice good healthy lifestyle habits to enhance your health. In addition, embrace the benefits of what we have learned about maintaining hormone levels and natural supplements to enhance these benefits. Here’s a short list:

1) If you’re weight is normal, keep it that way. Don’t allow yourself to gain weight. If you’re overweight, lose the extra pounds. We’ll talk more about this shortly

2) Exercise regularly and keep moving daily. Vigorous exercises for 30 minutes a day is probably one of the best things you can do to prevent Alzheimer’s disease. Exercise also improves heart health, and the better your heart health, the less you may develop Alzheimer’s disease. You can potentially reduce your risk of developing Alzheimer’s disease by 60% to 70% if you start in your 40’s and concentrate on keeping your body fit.[1] An added benefit is that keeping yourself fit also improves your attractiveness.

3) Next take supplements that reduce ROS and reduce inflammation within your body. There are a variety of supplements you can take that can do this. Concentrate on anti-inflammatory compounds and fat-soluble ones, like omegas, CoQ10, curcumin, and Vitamin D. Water soluble ones may include green tea and vitamin C.

4) When you reach middle age, especially if you become symptomatic from menopause or andropause, improve your quality of life and your health by maintaining adequate hormone levels. Starting early with hormone therapy has been shown to decrease your risks of developing not only Alzheimer’s disease, but also cardiovascular disease.

5)Other actions that may prevent ROS and inflammation in your body include stress reduction, adequate sleep habits, staying social, and maintaining good sex throughout your life. All are good for the soul, so when you nourish your sole and send good feelings within with a positive attitude, good things come to you. All these improve your quality of life, plus they may help prevent this root cause of Alzheimer’s disease.

Lose Weight and Eat Right

The first action you can do to prevent AD is to lose weight if you’re overweight and to eat right. If you’re overweight or obese during midlife you increase your risk of developing AD by 59%.[2] Then if you develop diabetes plus your cholesterol and your blood pressure is high, your risk increases for developing AD is six-fold higher than the normal risk. High blood sugars result in excess ROS and inflammation everywhere, including the brain. Elevated blood glucose and high insulin levels have been shown to be toxic to brain cells and cause further ROS formation.

If you become diabetic or even prediabetic, this destruction occurs in the small vessels that feed all your organs and cells, called your microvascular system. These are all the small capillaries in your brain, your eyes, your kidneys, and everywhere else. The ROS that injures these tiny vessels due to these changes from diabetics results in inflammation of these capillaries, thus it is called a microvascular disease.

The damage that occurs to this microvascular system in diabetics causes the symptoms you see in diabetics, including the destruction of cells in the kidneys resulting in kidney failure, or the destruction of cell structures in the back of the eye, the retina, resulting in blindness. The destruction to the microvasculature that feeds nerve cells results in the numbness in the hands and feet you see in diabetics, called peripheral neuropathy.

A similar destruction occurs in the brain, and this is called Alzheimer’s disease. The incidence of AD in diabetes is so high that some doctors have actually called Alzheimer’s disease Type 3 diabetes. There is no question that the high blood sugars and high insulin levels are toxic to the brain, so you must stop this destruction before it happens.

Hemoglobin A1c and Diabetes

There is a blood test you can do that will tell you if you are starting to develop diabetes. This blood test is called hemoglobin A1C (HA1C). It is the level of the hemoglobin in your red blood cells that have excess glucose attached on to it, called glycation. You want the levels to be below 5.0. Levels between 5.7 and 6.3 are considered prediabetic, and levels > 6.4 are considered diabetic.

HA1C is a great awakener to let you know that you must change your lifestyle if you want to prevent diabetes and its sequelae (including AD) from ruining your life. Being overweight can increase levels and if you stay overweight or obese the level of HA1C continues to rise because the process of ROS and increased inflammation progress if you don’t correct them early.

This destruction is the destruction of your microvasculature. Yes, it can start even though you’re not diabetic. It probably has started at least when you are prediabetic, but it gets worse as the disease progresses.

It may happen even in those who maintain a normal weight. Interestingly, HA1C can be mildly elevated in around 10% to 20% of people with normal weight. Thus, it is a good idea to have this test done even if you’re at a normal weight. If you are one of these, then what do you do? It’s not like you can lose weight because you’re already at a normal weight. But there is something you can do.

Maintain a Keto-Medi Diet

You probably have heard of a Mediterranean Diet and that it has been associated with a decreased risk of developing heart disease and other chronic medical illnesses.[3] Some studies suggest more than a 30% reduction. This diet is different than the Standard American Diet (SAD) by emphasizing eating more fish while minimizing beef. Eating more vegetables and lot of fats, but primarily good fats is common. But what you may not know is that increasing fat intake even more than in a typical Mediterranean diet reduces these problems even more.[4]

A high fat diet is a ketogenic diet where you eat mostly fat for your body’s fuel needs. The fat consumed, and the extra fat in your body and the byproduct of this is ketones. Ketones are another energy source for your body and your brain. In fact, your brain cells utilize ketones better than they do glucose. In addition, ketones act like growth factors to brain cells and stimulate the formation of new brain cells.[5] Remember, retaining a memory requires the formation of new brain cells and you can do this even better by maintaining a good level of ketones in your brain.

One way to maintain ketones in your blood is to do a ketogenic diet. Here, you consume 70% to 80% of your calories in the form of fats. But the best ketogenic diet encourages the use of good fats instead of bad fats. Good fats are in olive oil, olives, nuts, and naturally formed fats such as butter, cream, or coconut oil. Bad fats are hydrogenated vegetable oils or excess beef fat.

Reducing your carbohydrate (carb) intake is essential in doing any type of ketogenic diet. Carbs must be reduced to less than 5% to 10% of your total calories. In addition, eating a lot of protein is not necessarily a ketogenic diet. Protein should be limited to around 15% of total calories. It’s all about the fats, but emphasis on the good fats.

Studies have shown that maintaining ketosis can decrease your risks of developing Alzheimer’s disease.[6] They do this by decreasing ROS and inflammation which is toxic to brain cells and is responsible for the destruction of the brain cells and formation of inflammatory tangles as seen in Alzheimer’s patient’s brains.

With less destruction of neural tissues, ketogenic diets decrease the deposition of amyloid on the brain cells which is associated with AD. In addition, they improve the circulation of blood to the brain, which improves your heart health. And, as stated previously, improving heart health is one of the most important actions you can do to prevent AD. We will discuss this more in Part 3 of this series.

Summary

There is a plethora of actions you can embrace that will help decrease your risks of developing Alzheimer’s disease. These include losing weight and eating right. Reducing your weight can reduce your risk of developing AD significantly. Get your hemoglobin A1C level tested, even if you’re not overweight. It can be a sign that you should embrace better lifestyle changes, including a more ketogenic and Mediterranean diet. These may not only improve brain function and decrease risk of development of AD, but they may also improve cardiovascular health, which we will discuss next.

 

References:

[1] abia, S, et al. Association of ideal cardiovascular health at age 50 with incidence of dementia: 25-year follow-up of Whitehall II cohort study. BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4414

[2] Alford S, et al. Obesity as a risk factor for Alzheimer’s disease: weighing the evidence. Obesity Reviews. October 2017. 19(2). https://doi.org/10.1111/obr.12629

[3] Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and metaanalysis. Am J Clin Nutr 2010;92:1189- 96. https://academic.oup.com/ajcn/article/92/5/1189/4597540

[4] Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med, April 2013;368(14):1279-1290 . DOI:10.1056/NEJMoa200303.

[5] Lange KW, et al. Ketogenic diets and Alzheimer’s disease. Food Science and human Wellness. 6(1), March 2017: 1-9. doi.org/10.1016/j.fshw.2016.10.003

[6] IBID. doi.org/10.1016/j.fshw.2016.10.003

Robert True

The Brain Protecting Effects of Quercetin 

Quercetin, an isoflavone with a multitude of health improving properties, has been shown to protect your brain from some of the causes of chronic neural degeneration, called neural protection. This neuroprotection includes boosting the health of your arteries that feed the brain, enhancing mitochondrial functions to maintain good energy production to the brain, reduction in ROS, and anti-inflammatory properties,

Quercetin is found in many foods including apples and onions. However, most people don’t ingest enough quercetin to give themselves the power of quercetin to improve their brain health. Thus, supplementation is recommended. With adequate levels of quercetin in your blood, you may be able to protect your brain from chronic damage that could lead to chronic medical diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and other degenerative brain diseases you might get as you get older.

Feed Your Brain the Right Stuff

Arterial health is probably one of the most important things you can do to keep your brain healthiest. Poor arterial health, formation of cholesterol plaques with the arteries (atherosclerosis), development of inflammation within the endothelium, scarring, and hardening of the arteries (arteriosclerosis), is associated with brain health. Heart disease is associated with brain disease.[1] After all, if you improve the flow of blood to the brain you get better brain function.

Prevention thus first starts with ensuring a healthy heart. This includes making sure you are eating the right diet, such as a Keto-Mediterranean Diet. Exercising improves circulation to all body parts, including your brain, and exercising around 20 minutes a day is probably the most important thing you can do for your brain. Reducing stress and getting enough sleep are important too. Another beneficial action you can do is to make sure you ingest adequate amounts of quercetin.

How Alzheimer’s Disease Develops

There are many theories regarding how chronic degeneration of the brain occurs resulting in Alzheimer’s disease (AD), or Parkinson’s disease (PD), or other degenerative diseases. With AD, the process starts in your 40’s to 60’s, twenty years before you see the actual symptoms of AD. Most experts have concluded that AD starts with oxidative stress to the cells, particularly to the mitochondria of each cell.  This mitochondrial damage triggers and immune response from the immune cells near the brain cells (called microglia) and when this response is severe, inflammation occurs. Inflammation then causes destruction of neural cells, forming inflammatory tangles, and deposition of beta-amyloid on the nerve cells. When this progresses to a severe state over many years, Alzheimer’s disease is diagnosed. Preventing these from happening years before AD develops is key to prevention of AD.

Reduce Oxidative Stress to the Brain

The neuroprotective effects of Quercetin begins with reducing ROS. Constant excitatory electrical stimulation of the nerves cells through normal thought processes is considered to be the cause of oxidative stress (ROS) to the brain’s mitochondria, the powerhouses of neural cells, their mitochondria.[2]

Quercetin protects brain cells from the oxidative damage seen by the repeated excitatory electrical impulses and thus oxidative damage to the mitochondria of the nerve cells.[3] It increases expression of a natural cellular defense against such mitochondrial damage called the Nrf2 system, which help prevent brain cell death.[4] In addition, quercetin’s anti-oxidant and anti-inflammatory actions reduce toxicity of the dangerous and abnormal beta-amyloid proteins onto the nerve cell walls, which are thought to produce the symptoms of memory loss and dementia.[5]

Moreover the damage to the nerves through these processes results in destruction of the brain structure seem in dementia diseases such as AD and Parkinson’s disease.[6] Quercetin has been found to prevent brain cell death in animal models of Parkinson’s disease.[7]  It preserves vital brain cell function and limits brain cell death that would otherwise produce neurodegenerative diseases.[8]

Increase in Mitochondria in Brain Cells

Studies also demonstrated increased formation of mitochondria in brain cells with administration of quercetin in animal studies.[9] An increase in brain mitochondria increases energy to the brain cells with accompanying increase if brain function. Along with a decrease in ROS, this could confer protective effects of the brain from developing Alzheimer’s disease and other chronic neurodegenerative diseases, of which mitochondrial dysfunction are hallmarks.

Summary

Quercetin can help protect the brain from developing Alzheimer’s disease. It does this through many pathways, including decreasing ROS damage to mitochondria, increasing the number of mitochondria, and decreasing inflammation. Start early and make sure you are getting adequate amounts of quercetin, either through your diet or by taking supplements.

 

These statements have not been evaluated by the Food and Drug Administration (FDA). Any products are not intended to diagnose, treat, cure, or prevent any disease.
References:

[1] Sabia, S, et al. Association of ideal cardiovascular health at age 50 with incidence of dementia: 25-year follow-up of Whitehall II cohort study. BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4414

[2] Dorszewska J. Cell biology of normal brain aging: synaptic plasticity-cell death. Aging Clin Exp Res. 2013 Apr;25(1):25-34. doi.org/10.1007/s40520-013-0004-2

[3] Silva, B., Oliveira, P.J., Dias, A. et al. Quercetin, kaempferol and biapigenin fromhypericum perforatum are neuroprotective against excitotoxic insults. neurotox res 13, 265–279 (2008). https://doi.org/10.1007/BF03033510

[4] Arredondo F, Echeverry C, Abin-Carriquiry JA, et al. After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult. Free Radic Biol Med. 2010 Sep 1;49(5):738-47. doi.org/10.1016/j.freeradbiomed.2010.05.020

[5] Shi C, Zhao L, Zhu B, et al. Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against beta-amyloid peptide-induced toxicity in SH-SY5Y cells. Chem Biol Interact. 2009 Sep 14;181(1):115-23. doi.org/10.1016/j.cbi.2009.05.010

[6] Week GL, McGann-Gramling K, Hauss-Wegrzyniak B, et al. Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid. J Neurochem. 2004 Apr;89(2):484-93.

[7] Karuppagounder SS, Madathil SK, Pandey M, Haobam R, Rajamma U, Mohanakumar KP. Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson’s disease in rats. Neuroscience. 2013 Apr 16;236:136-48.

[8] Bournival J, Plouffe M, Renaud J, Provencher C, Martinoli MG. Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system. Oxid Med Cell Longev. 2012;2012:921941.

[9] Op cit. Davis, m, et al. doi.org/10.1152/ajpregu.90925.2008

Robert True

Alzheimer’s Disease, Part 1: How does it Happen?

What causes Alzheimer’s disease (AD)? You have probably seen older people with Alzheimer’s disease and know that it is a progressively crippling disease with mental deterioration, ending finally in total disability and spiraling down to debilitating frailty and death. Not a pretty site for most people. Or you may have a family member, like your mom, who may have developed this and you ask, “How did you get this, Mom?” What could you have done to prevent it?

To understand what you can do to prevent this devastating disease from happening in you, you must understand two things: 1) How the disease forms and progresses, 2) What you can do to prevent the disease. There is no treatment of the disease at present. Your best action is to do all the things needed to prevent the disease. You should start prevention early and not wait until you’re over the hill, so start now, even if you are only 30 years old.

How does Alzheimer’s disease start to happen?

If you look at a brain of a person with AD through the microscope you would see several changes to the neurons that are not supposed to be there. You would see clumps of a sticky substance called amyloid that appear to be stuck on the nerve cells in an irregular fashion. You also would see the presence of Inflammatory tangles, which kind of look like a wad of fishing line all tangled up.

At one time it was thought that the amyloid was toxic to the cells and when accumulated on the neurons it resulted in the damage that results in AD. This may be the case in the inherited form of AD (i.e. young onset; around age 50) but may not be the case in the most common form of AD that forms as you get older.[1] It may actually be an attempt to repair the cells, but too much damage occurs so you get too much sticky gum on the neurons possibly slowing their conduction.

The incidence of AD is around 10% of the general population, most of which is the common type. It is the one that you see in older people, generally at least over the age of 55. The hereditary form comprises only about 1% of the cases of AD, and generally occurs when the person is younger, i.e. under the age of 55. Both end up with the same devastating debilitation that you see with AD. Since we can do something about the most common form, we’ll discuss that one.

It is now thought that AD starts with metabolic stress in the brain. This is essentially the formation of excess free radicals within the cells and, specifically, the mitochondria within the cells. The mitochondria are the powerhouses of the cells. They are continually exposed to constant electrical activity to make our power molecules (ATP), which is their main function

Think of mitochondria like a power plant that’s producing electricity. The electricity powers mechanical stuff that we use by the flow of electrons through the wires. However, occasionally “shorts” happen, which can damage the wires and anything that’s near it. Have you ever shorted out something and saw the damage? That’s what we’re talking about.

The mitochondria produce energy in the form of ATP. This is a highly energized molecule that fuels every function of your body, from moving your arms to thinking about your next conquest. ATP is like the electricity of your cells. During its formation, free electrons may form called reactive oxygen species (ROS), which can damage structures, like the short at the electrical plug.

It is now thought that AD starts by the excess formation of these ROS, which then damage the cellular structures near it, which may be the membranes, DNA, mitochondria per se, or other tiny structures within the cells. Microscopically, this damage then sets up a cascade of events which, if not corrected properly, may result in AD within the brain.

ROS Triggers Amyloid Production and Inflammation

Your body was built to repair itself down to the micro level. If you cut yourself, your body repairs the cut. If you bruise yourself, your body dissolves the bruise. What’s not right your body has systems that repair it and correct the problem. This is you immune system at work. At the cellular level, if ROS damages your mitochondria and the surrounding parts of the cell, your body’s reparative actions are triggered to repair the damage and make it better.

This reparative process includes two actions within the brain. The ROS damage triggers the cells to produce amyloid, sort of like a sticky band aid on the damaged neuron, and it triggers cells within the brain called microglia to fix the damage. These microglia are part of your immune system, which does a plethora of actions from identifying a problem, sending cells to fix the problem, and cleaning up the mess from the problem.

Part of the mess is the amyloid. The microglial cells are the brain’s macrophages: they literally eat up the mess. They are like an army of cells that swarm around the amyloid accumulations, called plaques. Essentially, they invade the plaque and try to repair the damage while cleaning up the damage, which results in a lot of collateral damage and accumulation of inflammatory cells, otherwise called inflammation.

You have probably seen people who have inflammation of their hands due to arthritis. Their fingers become inflamed with pain. The result is destruction of the joints, which then causes deformities of the joints, debilitation, and even more pain. Pain can be a sign of destruction of the tissue. However, in the microscopic environment of the brain, you don’t feel the pain. Thus, you don’t feel the destruction that may be happening there. And the destruction that leads to AD can begin 20 years or more before you actually see symptoms of AD.

The inflammatory damage causes further destruction to the nerve cell walls, called the cytoskeleton of the cells, and ultimately these walls collapse. Nerve cells are long, like microscopic fishing line, with a tiny body sending out the signals. When the damage to the exoskeleton is severe, the cell collapses and forms into a tangle of fibers called neurofibrillary tangles. These look like small tangled clumps of fishing line. Of course, when they happen, the neuron is dead and functions no more.

After a lot of these neurofibrillary tangles form from the excess ROS damage, you start to see a significant amount of brain dysfunction. Your memory becomes bad and you just are not able to function adequately in this world. As this process continues, your mind goes. You don’t think well, you don’t remember things and people, and ultimately the destruction of the brain cell results in the frail AD patients that you may have seen who die through a slow sad death spiral.

Since none of us wants to suffer from this, there are things that you can do to prevent this destruction from happening, which we’ll discuss in Part 2 of this series. (TO BE Continued)

[1] Geldmacher DS. Alzheimer disease prevention: Focus on cardiovascular risk, not amyloid?. Cleveland Clinic Journal of Medicine. 77(10). Oct 2010:689-704. https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/issues/articles/media_e3acdb4_689.pdf

Robert True

Quercetin’s Heart Protective Mechanisms

Quercetin is a supplement from red wine and other fruits that has been studied for decades and found to protect your body against age-related disorders. It particularly is beneficial to improve the health of the inner linings of your arteries, called the endothelium. It may prevent many destructive factors of aging through its anti-inflammatory and antioxidant qualities. Taking quercetin has long been considered a broad-based anti-aging strategy.

Quercetin is a natural compound found in many foods, such as onions, parsley and apples. Remember the old saying, “Eat an apple a day to keep the doctor away.” However, most people don’t ingest enough apples or other foods to provide them with the power of quercetin to improve their heart health. You may need to supplement your nutrition with quercetin. Having adequate levels of quercetin in your blood can improve the health of your heart and blood vessels in many ways.

Endothelium Damage and Cardiovascular Health

Plaques may form under the endothelial lining of the arteries in a known fashion. First a cell lifts slightly, possibly due to the forces of the blood running through it. The more force is presented with this flow, such as with high blood pressure, the more likely damage to the endothelium may occur.

Once slightly lifted, if you have a lot of bad cholesterol, the tiny granules of cholesterol in your blood, these can rapidly accumulate below the endothelial cells and form plaques. These undergo oxidative damage and the development of oxidative damage, called reactive oxidative species (ROS) which damages the endothelial cells.

Your body tries to repair this damage and sends in immune cells. If overwhelmed, inflammation occurs resulting in further damage. This inflammation, when severe, can result in liquefaction of the plaque, rupture, and potentially clotting of the artery. This is not a good thing for the heart and the brain, for a heart attack and/or a stroke can then happen that is life threatening.

Quercetin Improves Arterial Health

Quercetin helps improve endothelial health through several mechanisms. When the endothelium is improved, health of the heart is also improved. Think about when you or someone you know has complaints of chest pain. What do the doctors check? They evaluate the arteries that feed the heart. Thus, improving arterial health correspondingly improves heart health.

Dietary flavanols and flavones such as quercetin have a significantly lower risk for developing vascular diseases for good reasons. Quercetin helps prevent this through many mechanisms. Quercetin is considered a polyphenol and these reduce ROS and inflammation in the body, including the endothelium.

Studies show a regression of atherosclerotic plaque by quercetin through many mechanisms. It triggers transport of cholesterol from the arterial wall by using your good cholesterol HDL. HDL has been shown to improve heart health through its ability to take cholesterol away from the deposits of cholesterol and transport them to the liver for safe disposal. [1],[2] The higher your blood level of HDL, the more likely you can transport these bad deposits away from your endothelial walls before build-up occurs.

However, once inflammation sets in you got trouble. But quercetin may decrease the ROS that forms, including the mitochondrial ROS excess before it can cause excess damage[3] Quercetin also inhibits some of the inflammatory enzymes that cause further damage. These include COX-2, which forms prostaglandins and cause inflammation and pain; MMPs, metalloproteinases that dissolve tissue; and 5-LOX, which forms inflammatory compound such as leukotriene. These are the enzymes that produce the pro-inflammatory molecules that can destroy the tissues of the arteries and form the plaques. [4], [5]

Quercetin also restores normal production of nitric oxide, which is important for relaxation of arterial muscles to allow them to dilate and improve blood flow.[6] This is particularly important in those with high blood pressure. If you can relax your arteries better and they are not so “stiff”, you could reduce hypertension and coronary artery disease.[7] One human study showed that a quercetin-containing food improved after-meal endothelial function by 31.4%.[8]

Improving endothelial health equates to better heart health. The chest pain person we discussed gets an evaluation of their heart vessels through an angiogram, where they use a special x-ray and die to see the vessels of the heart. If plaque have formed and is constricting the arteries that go to the heart, that’s bad. They can stent them or do a bypass surgery, but the best plan is to start in your 40’4 to 50’s and prevent the problem. One method is to boost your quercetin levels.

Heart Protection with Quercetin

Studies have shown that long term ingestion of dietary flavanols and flavones such as quercetin have a significantly lower risk for developing cardiovascular diseases.[9] Quercetin is considered a polyphenol, and these reduce ROS and inflammation in the endothelium. In addition, mitochondrial ROS is also reduced while the number of mitochondria in muscle is increased.

Looking at a human study, men who took 1,000 mg/day of quercetin for just two weeks were able to increase the distances they could run on an increase in mitochondria in the muscle. Mitochondrial numbers grew in the muscles by 4.1% in supplemented group, while falling 6% in the placebo group.[10]

In a mouse study, giving quercetin for just seven days showed a biopsy proven increase in the formation of new mitochondria in the muscles and brains of the mice.[11] Along with this increase was an increase in exercise endurance of the mice taking quercetin versus those not taking it. This finding would correlate with the increase in mitochondria that quercetin induced.

Conclusion

One of the many dietary nutrients that you can take that may improve your heart health is Quercetin. It has many effects that prevent endothelial destruction and formation of plaques, but once these happen, devastating heart disease can take hold. Start boosting quercetin levels in your body early, either with a good diet or supplements to ensure adequate levels. Continue this as a part or your regiment to improve the health of your blood vessels, and in turn this will improve your heart health.

 

These statements have not been evaluated by the Food and Drug Administration (FDA). Any products are not intended to diagnose, treat, cure, or prevent any disease.

References:

[1] Ohara K, Wakabayashi H, Taniguchi Y, Shindo K, Yajima H, Yoshida A. Quercetin-3-O-glucuronide induces ABCA1 expression by LXRalpha activation in murine macrophages. Biochem Biophys Res Commun. 2013 Nov 29;441(4):929-34. doi.org/10.1016/j.bbrc.2013.10.168

[2] Lee SM, Moon J, Cho Y, Chung JH, Shin MJ. Quercetin up-regulates expressions of peroxisome proliferator-activated receptor gamma, liver X receptor alpha, and ATP binding cassette transporter A1 genes and increases cholesterol efflux in human macrophage cell line. Nutr Res. 2013 Feb;33(2):136-43. doi.org/10.1016/j.nutres.2012.11.010

[3] Davis JM, Murphy EA, Carmichael MD, Davis B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1071-7. doi.org/10.1152/ajpregu.90925.2008

[4] Bhaskar S, Kumar KS, Krishnan K, Antony H. Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits. Nutrition. 2013 Jan;29(1):219-29. doi.org/10.1016/j.nut.2012.01.019

[5] Scoditti E, Calabriso N, Massaro M, et al. Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer. Arch Biochem Biophys. 2012 Nov 15;527(2):81-9. doi.org/10.1016/j.abb.2012.05.003

[6] Shen Y, Ward NC, Hodgson JM, et al. Dietary quercetin attenuates oxidant-induced endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: A critical role for heme oxygenase-1. Free Radic Biol Med. 2013 Dec;65:908-15. doi.org/10.1016/j.freeradbiomed.2013.08.185

[7] Fitzpatrick DF, Hirschfield SL, Coffey RG. Endothelium-dependent vasorelaxing activity of wine and other grape products. Am J Physiol. 1993;265:H774-8. /doi.org/10.1152/ajpheart.1993.265.2.H774

[8] Nakayama H, Tsuge N, Sawada H, Higashi Y. Chronic intake of onion extract containing quercetin improved postprandial endothelial dysfunction in healthy men. J Am Coll Nutr. 2013;32(3):160-4. doi.org/10.1080/07315724.2013.797858

[9] Scoditti E, Calabriso N, Massaro M, et al. Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer. Arch Biochem Biophys. 2012 Nov 15;527(2):81-9. doi.org/10.1016/j.abb.2012.05.003

[10] Nieman DC, Williams AS, Shanely RA, et al. Quercetin’s influence on exercise performance and muscle mitochondrial biogenesis. Med Sci Sports Exerc. 2010 Feb;42(2):338-45.

[11] Davis JM, Murphy EA, Carmichael MD, Davis B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1071-7. doi.org/10.1152/ajpregu.90925.2008

Robert True

Peptides Part 6: Boost Your Energy

Peptides are compounds made from amino acids that signal your body to do certain functions. In this part of my series on peptides, I will discuss some peptides that can give you a boost in your energy.

It seems like fatigue is a common complaint of patients in my practice. There are many reasons why you might become fatigued, and first an evaluation to determine the reason for the fatigue is indicated. When problems are discovered, I first take care of the problem or problems.

Hormone Optimization and Body Metabolism

One of the most common reasons you may have fatigue is because you don’t have optimal levels of hormones. Thyroid hormones and testosterone both need to be optimized to give you the best boost in energy from these hormones. Testosterone must be balanced with estrogen in a woman for best results.

A simple blood test can tell you if your levels are low or suboptimal. If yours are low, you should consider supplementing low thyroid levels with thyroid hormones, and low testosterone levels with testosterone therapy to raise these hormone levels to more optimal levels. Having levels like you had when you were younger and you had that youthful vitality is a great plan.

In addition, there are other reasons why you may be having fatigue problems, and one of these is that you may just be overweight. Dragging around extra weight can make anyone tired and fatigued. Thus, an important action you can do is to get rid of that extra weight. You’ll be amazed at how great you’ll feel when you get rid of that spare tire that’s weighting you down.

Although it seems like an oxymoron, exercising also can improve your energy and reduce fatigue. When you drag yourself to the gym, think about this: you may not like exercising, but you will like the way it makes you feel. Vigorous exercise for just 10 to 12 minutes a day may boost your metabolism to help make you feel stimulated and energetic.

Boost Energy with Growth Hormone

Another hormone that declines as you get older is growth hormone. I have discussed growth hormone stimulation via peptides in another article. I do not recommend direct injections of HGH. Boosting growth hormone levels improves energy production and decreases fatigue, but you want to do this in a natural physiologic way, like with peptides that stimulate your pituitary to produce more growth hormone.

In addition, using the peptides to do this does a bunch of other actions too. Growth hormone can also increase muscle mass so you’re stronger, decrease fat mass so you lose weight, and improves your thought process so you think clearer. It may also have anti-aging actions, which may help you live longer.

Age-Related Fatigue and Mitochondria

Another reason that may be causing your fatigued has to do with the natural age-related decline in energy production that occurs as you age. Your body must produce energy for all the functional processes of your body; to move, to think, to beat your heart, to digest food, etc. This energy comes from your mitochondria, the powerhouses of your body.[1] These nanosized parts of your cells are like your power houses that produce the energy for your body.

Just like the electric powerhouses that produce electricity to power all the lights and machines close to it, your mitochondria produce ATP which are packets of energy that power all the functions and parts of every cell in your body. In addition, just like electric energy sometimes can spark and cause damage, so can the byproducts of energy production in your cells.

This continued process of damage to your mitochondria results in aging of your body.[2] With less energy production you become more tired, of course.  But the cells of your organs also suffer from this low energy and this can result in age-related chronic medical disease problems. For instance, one of the initial problems with dementias such as Alzheimer’s disease is a sluggishness in thought process. This has been associated initially with the increase in ROS production that damages brain cell mitochondria.

This mitochondrial damage occurs due to formation of free radicals (ROS) from normal functions of the mitochondria to produce energy (ATP) for the cell. Mitochondria produce a compound that protects the mitochondria from the damaging effects of ROS in a natural fashion, which is a good thing otherwise none of us would be able to keep our energy production going. This compound is a natural peptide.

MOTS-c Peptide for Energy

This natural peptide that protects the mitochondria from ROS damage is called MOTS-c. In addition, MOTS-c can stimulate your mitochondria to produce more mitochondria in addition it regulates gene expression to increase their production.[3] All this results in more ATP production, which equates to more energy and less fatigue. Moreover, if you can boost your energy productions as you age, you may have a more active life and potentially live longer too. Thus, MOTS-c may ultimately correlate with extended longevity.[4]

Due to its effects on the mitochondria, MOTS-c has also been shown to improve insulin regulation and metabolic homeostasis, improving insulin resistance, reducing diabetes[5] and help patients lose weight.[6] This may improve processes such as aging, inflammation, and stress resistance. Mitochondrial dysfunction contributes to abnormal sugar metabolism in diabetes and is thought to be part of the destruction from diabetes.[7]

In essence, you are simply using MOTS-c, which is actually produced by the mitochondria’s own DNA, to protect the mitochondria from age-related degradation. The result is that you get a boost of energy production from your own mitochondrial powerhouses.

Dose: MOTS-c Comes in a 10 mg vial. After reconstituting the vial with sterile water, 10 mg is injected subcutaneously into the skin weekly for the usual dose. Unfortunately, this injection may burn for a few minutes, but this does go away and does not injure the tissues.

Summary:

Boosting energy production to reduce fatigue is a multifactorial process involving optimization of many hormones, losing weight, eating right, and exercising. Boosting levels of growth hormones with peptides decreases fatigue too. Energy production is done by your mitochondria. Boosting protection of the mitochondria from ROS, the production of mitochondria, and the production of ATP by mitochondria is important.

MOTS-c is a peptide that can potentially boost all these mitochondrial actions to help you have more energy. In addition, as you age, energy production from mitochondria decrease and this is thought to be partly the cause for development of age-related chronic medical problems. Boosting mitochondrial functions with MOTS-c peptide could help protect you from these conditions while enhancing your energy levels.

References:

[1] Filler K, et al. Association of mitochondrial dysfunction and fatigue: A review of the literature. BBA Clinical. 1, June 2014:12-23. doi.org/10.1016/j.bbacli.2014.04.001

[2] Kim, Su-Jeong. Et al. Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging (Albany NY), 10(6) June 2018: 1239-1256.

[3] Lee C, et al. The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance. Cell Metabolism. 21(3) March 2015:443-454. doi.org/10.1016/j.cmet.2015.02.009

[4] Fuku N, et al. The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity? Aging Cell (2015) 14, pp921–923. doi.org/10.1111/acel.12389

[5] Lee C. et al. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radical Bio and Med. 100, Nov 2016:182-187. doi.org/10.1016/j.freeradbiomed.2016.05.015

[6] Op cit. Lee C. doi.org/10.1016/j.cmet.2015.02.009

[7] Ramanjaneya M. et al. Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects. Front. Endocrinol., 31 May 2019 | https://doi.org/10.3389/fendo.2019.00331

Robert True

Peptides Part 5: Hair Growth and Skin Rejuvenation

Peptides stimulate multiple processes to occur in your body that can help you in many different ways depending on the peptide use. There are many peptides that can improve your looks, improving your hair growth and the health of your skin, with equates to more attractive skin.

Hair Loss and Peptide Use

There is no cure for baldness since here the follicles are essentially non-functioning and not viable. However, if you have follicles present that are still functioning, perhaps all you need to do is to stimulate their growth so they can help you have a fuller, richer head of hair. This is the potential action that certain peptide can do for you.

There are four peptides that can potentially help you grow more hair. We have already discussed Thymosin Beta 4, which can decrease inflammation. If the problem of hair loss is due to some inflammatory condition, this peptide should help. It also stimulates formation of vessels to feed the hair follicles better. If you feed something well, it will tend to grow more. Plus, if there is inflammation in your body, this peptide may help this too and make you feel better. Thymosin Beta 4 may also stimulate stem cells to grow more hair.[1]

Another similar peptide is Thymulin, which is also a peptide of the thymus gland. But it also is formed by your hair follicles to stimulate and regulate hair growth. The activity of thymulin to stimulate hair growth is dependent on the presence of Zinc. Thus, you’ll see thymulin combined with zinc in most products, which are usually topical agents applied to the scalp.

There are two other peptides that are particularly unique to stimulation of hair growth. On is also good for the skin while the other specifically can help in hair loss that is due to androgenic blockage of hair growth

GHK-Cu: Good for Hair and Skin

When applied topically, this peptide is good not only for decreasing hair loss and stimulating hair growth, but it also can improve your skin. It increases hair follicle size and helps with hair loss. It provides these actions thought several mechanisms: it stimulates dermal fibroblasts, it increases the expression of certain growth factors, and combined with copper stimulates formation of other factors that improve the health of your skin.[2]

The combination can promote activation of wound healing, improve the immune response in the area, and act as antioxidants and anti-inflammatory agents. It also stimulates collagen and glycosaminoglycan synthesis in the skin fibroblasts, improving the health and integrity of the skin and hair follicle. In addition, it stimulates growth of blood vessels to better feed the follicles so they can grow better. Studies have shown increased growth of hair.[3]

It does similar actions on your facial skin when applied there, and therefore is great for facial rejuvenation too. By improving collagen, fibroblasts and other structures under the skin, GHK-Cu can also improve the texture of your facial skin (tighten pores in the skin), decrease fine lines and wrinkles, and improve the general health of your skin.

Fibroblasts are the workhorses of the skin. They form type 1 collagen, hyaluronic acid, elastin and other proteins that keep your skin healthy and looking younger. Unfortunately, as you age your fibroblasts slow down and there’s less of them, resulting in aging of the skin. Fortunately, this peptide mixed with copper stimulates fibroblasts to do their thing, resulting in more youthful looking skin.

It can also accelerate healing of the skin, [4] so it is also great for post procedure use, such as after microneedling or resurfacing procedures. It also can help tighten the skin, improve skin elasticity, skin density and firmness.

Thus, GHK-Cu signals fibroblasts and other structures of the skin resulting in an increase in hair growth on the scalp and a more youthful appearance of you skin. Note that it does not increase facial hair growth in women, so don’t worry about you growing a beard if you’re a woman.

PTD-DBM: for Androgenic Hair Loss

Many women complain that their testosterone therapy is making them lose their hair. In most women, testosterone therapy, when done correctly with dosage increased gradually, see the opposite effect; they see increased scalp hair growth. However, some women are susceptible to a problem called androgenic alopecia, where testosterone can actually thin the hair through hair loss.

In this condition, certain medications can help prevent and reverse this sensitivity to testosterone. These can include spironolactone and finasteride. If you suffer from this problem and want to continue taking your testosterone because you like the way it makes you feel, then you should take these medications to help prevent the hair loss.

There is also a peptide that can help this type of hair loss call PTD-DBM, but we’ll shorten the name to PTD. This peptide was originally discovered in Korea when males pattern baldness was treated by it with very good results. In a nutshell, this type of hair loss is caused by increased levels of a compound called CXXC5. PTD inhibits the effects of this compound on the hair follicle to prevent hair loss.[5]

Adding another compound to this, valproic acid, boosts the ability to prevent this type of hair loss several fold. However, in order to be effective, you have to apply both preparations separately. The costs of this treatment are also higher than other peptide treatments.

Dosage: GHK-Cu may be applied to the skin or scalp through multiple routes. A foam can be applied to the scalp or skin once daily at night, using 2 pumps of the foam (1 ml). It is also available as a cream to applied to the face each bedtime.

Alternatively, GHK-Cu can be injected into the scalp via small needles or microneedling techniques. This can be combined with PRP injections into to scalp or alternate with these treatments to boost the growth of your hair follicles and hair growth.

PTD-DBM is available in a spray bottle and the hair can be sprayed once daily on the area for intended hair growth.

Summary:

There are several peptides that can not only improve growth of hair and decrease hair loss but can also improve skin health. All work on improving the growth of blood vessels to them, stimulating fibroblast growth and function, and other mechanisms of action. They can markedly help those who suffer from hair loss, whether from aging or from androgenic hair loss, plus reverse the aging process of the skin to preserve more youthful appearance of the skin.

 

References:

[1] Philp D, et al. Thymosin Beta 4 Induces Hair Growth via Stem Cell Migration and Differentiation. Cell Biology Section, NIDCR, HIH, Bethesda, Maryland, USA. (link)

[2] Pickart L. et al. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. BioMed Research International. 2015, Article ID 648108. http://dx.doi.org/10.1155/2015/648108

[3] Lee WJ. Et al. Efficacy of a Complex of 5-Aminolevulinic Acid and Glycyl-Histidyl-Lysine Peptide on Hair Growth. Ann Dermatol. 2016 Aug;28(4):438-443. July 26, 2016.  https://doi.org/10.5021/ad.2016.28.4.438

[4] Simeon A, et al. Expression of Glycosaminoglycans and Small Proteoglycans in Wounds: Modulation by the Tripeptide–Copper Complex Glycyl-L-Histidyl-L-Lysine-Cu2+. Journ. Of Invest. Dermatol., 115(6) Dec. 2000: 962-968. doi.org/10.1046/j.1523-1747.2000.00166.x

[5] Lee SH. Et al. Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis. Journ of Invest. Erm. 137(11) Nov 2017: 2260-2269. https://doi.org/10.1016/j.jid.2017.04.038

Robert True

Peptides Part 4, Healing and Repair

Peptides are made of amino acids that tell the body’s cells to do certain functions. They are signaling compounds. One amazing peptide is called BPC-157 and it tells the cells and tissues to “Heal thyself”. It has been used in multiple settings of injury, damage and inflammation with very good results.

The potential uses of this peptide are extensive. They can signal improved healing in joint arthritis, ligament tears, tendonitis, and other orthopedic injuries. Other uses are regarding certain inflammatory medical conditions, such as Crohn’s disease or ulcerative colitis, lupus, and muscular sclerosis (MS). They also are cardio- and neuro-protective too and may prove valuable in many chronic age-related issues such as heart disease and Alzheimer’s disease.

Short History of BPC-157

This peptide was discovered over a hundred years ago in gastric juices (secretions from the stomach), but its function was not appreciated at that time. As you know, your stomach is in almost a constant exposure to hydrochloric acid that helps digest your food. If you were to put hydrochloric acid on your skin, it would burn a hole in your skin. So why doesn’t it burn a hole in your stomach?

The answer is complex, but part of it has to do with the fact that the cells in the lining of your stomach are continuously in a reparative mode. They always are fixing and reproducing more stomach cells because they are continuously being damaged by the hydrochloric acid. In addition, the tiny microvascular blood flow that feeds the cells is also injured along with the tiny nerves that stimulate the functions of the stomach, but these must get repaired too.

So, what stimulates all these different cells to quickly continually heal themselves? Much research suggests that it is BPC-157.[1], [2] This peptide is secreted by the stomach cells and sends signals to the cells of the stomach to essentially fix themselves: reproduce, repair, stimulate growth, and stimulate repair and formation of microvasculature and nerves. In a nutshell you could say that this peptide stimulates repair of damaged tissues.

Repair of Orthopedic Problems

Since BPC-157 can stimulate repair of tissues, it has been used to treat many orthopedic injuries, such as torn ligaments, muscles and tendons.[3] Injections can be made directly into the tissues and can accelerate healing. If many tissues are affected, subcutaneous injections can be done and the peptide will travel to the injury and stimulate the healing process to occur.

Tendons and ligaments heal better and faster. There is improved formation of tissues with an increase in fibroblasts, in collagen fibers, and other structures. Moreover, the structures are less inflamed, and they function at a significantly higher level. Growth factors that produce tissue components and make blood vessels grow into them are increased when the peptide is used.[4] You still need to go through a healing process, but peptides can potentially make them heal faster and better.

Arthritic process may also be stimulated to heal, resulting in repair of the inflamed joints. In addition, pain is decreased too by BPC-157. Thus, those who suffer from painful arthritis could benefit significantly from use of this peptide.

Healing of Inflamed Stomach and Intestinal Tissues

BPC-157 helps prevent ulcerations of stomach tissue by stimulating the healing response. It is thus not surprising that it can heal ulcers[5] and it scan be very beneficial in those autoimmune diseases that are complicated by ulcers of the intestines due to inflammation in those tissues. These can include ulcerative colitis, Crohn’s disease, and Irritable Bowel Syndrome.

One sees less oxidative stress in the tissues with less damage and improved cell survival with use of BPC 157. It increases tissue healing by increasing fibroblast activity, which forms the structures of the intestinal organs. In addition, it increases formation of new vessels into the gut tissues (angiogenesis) which improves blood supply to the tissues to help in the healing process.[6]

BPC157 has been shown to protect the gut from the adverse effects of alcohol and nonsteroidal anti-inflammatory drugs (NSAIDS), which have been shown to increase risk of gastric ulcers.  It also counteracts the effects of cancers to the body. It has been shown to decrease the cachexia, muscle wasting, and inflammatory reactions that are seen in cancers.[7]

Healing Heart and Neurological Damage

Much research has been focused toward improving the health of the vasculature in your body. These vessels must be very healthy to distribute the blood to all areas of your body, including your brain and your heart. BPC 157 has been shown to improve the health of the endothelium, which is the inside lining of all blood vessels.

Just like it heals the stomach, it can heal and repair damage to the endothelium, which subsequently helps to maintains a healthier state and protects the endothelium from further damage (cardioprotective). It can help improve the healing of endothelial tissue that had been damage by multiple mechanisms, including high blood pressure, clotting, thrombosis, etc. It dilates the vessels to improve circulation and stimulates the growth of new vessels.[8]

There has been much research on stimulation of the healing process by BPC-157 on the brain. It appears that it is neuroprotective and can also stimulate repair of neurological damage. It improves nerve regeneration, decreases inflammation of the neurons, and influences many neurotransmitter systems, including serotonergic, dopaminergic, opioid and GABAergic systems.[9]

Because BPC-157 appears to help stimulate the healing of damaged tissues and help in their regeneration, it may counteract the otherwise progressive courses of injuries to the neurons, including traumatic brain issues.[10] Moreover, because of its healing signaling, it is speculated that it may help in chronic age-related neurological issues such as Alzheimer’s disease or Parkinson’s disease.

Dosage: BPC-157 is usually given by an injection below the skin (SQ) at 0.15 cc to 3.0 cc daily. Normally improvement in healing of orthopedic problems is seen within 2 to 4 weeks of use of this peptide. A dose of 0.15 cc may be all that is necessary for long term protective effects.

Summary

BPC 157 is a peptide that stimulates the healing of tissues and can accelerate healing in multiple organs. It can help repair tendons, muscles and ligaments plus help heal arthritic conditions. It is very beneficial in healing gut issues and can help treat chronic inflammatory issues of the gut such as ulcers, Ulcerative colitis and Crohn’s disease. It is also protective for the brain and the heart. When damaged tissue is present, this peptide can help heal it and make this happen faster for better health and to improve your quality of life.

 

References:

[1] Sikiric P,    et al. Stable Gastric Pentadecapeptide BPC 157-NO-system Relation. Current Pharmaceutical Design, 20(7), 2014:1126-1135(10).

[2] Xue X-C. Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats. World J Gastroenterol. 2004 Apr 1; 10(7): 1032–1036. 2004 Apr 1. doi: 10.3748/wjg.v10.i7.1032

[3] Gwyer, D., Wragg, N.M. & Wilson, S.L. Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell Tissue Res 377, 153–159 (2019) doi:10.1007/s00441-019-03016-8

[4] Vukojević J, Siroglavić M, Kašnik K, Kralj T, Stanćić D, Kokot A, Kolarić D, Drmić D, Sever AZ, Barišić I, Šuran J (2018) Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157. Vasc Pharmacol 106:54–66. doi.org/10.1016/j.vph.2018.02.010

[6] Duzel A, et al. Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfuction in rates: new insights. World J Gastroenterol. 2017;23(48):846588. doi: 10.3748/wjg.v23.i48.8465

[7] Sikiric P, HahmKB, Blagaic AB, Tvrdeic A, Pavlov KH, Petrovic A, Kokot A, GojkovicS, Krezic I, Drmic D, Rucman R, Seiwerth S. Stable Gastric Pentadecapeptide BPC 157, Robert’s Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye’s Stress Coping Response: Progress, Achievements, and the Future.  Gut Liver. 2019 Jun 4. doi: 10.5009/gnl18490

[8] Sven Seiwerth*, Luka Brcic, LovorkaBateljaVuletic, Danijela Kolenc, GoranaAralica, MarijaMisic, Anita Zenko, DomagojDrmic, Rudolf Rucman and PredragSikiric, BPC 157 and Blood Vessels , Current Pharmaceutical Design, 2014, 20, 1121-1125

[9] Sikiric P, et al. Brain-gut axis and pentadecapeptide BPC 157: Theoretical and practical implications. Curr Neuropharmacol. 2016;14:857-65.

[10] IBID

Robert True

Peptides, Part 3: Enhance Your Sex Life

Peptides are chains of amino acids that signal microscopic actions within your cells to improve their efficiency and their functions. Certain peptides can enhance your sex life by acting in your brain to boost your libido, sexual desire, and satisfaction from sex. This occurs in both a man and a woman, plus they help men who have problems with erectile dysfunction (E.D.) Boost your mojo!

Low Sex Drive

Many women and men suffer from low sex drive. Much of this is due to low testosterone levels that occurs as you age and other factors that affect libido. Thus, the first thing you want to do if you have this problem is to make sure your hormones of estrogen and/or testosterone are boosted to optimal levels to help improve sex drive and performance. Getting a healthier body also helps, such as losing weight and eating right. However, sometimes this just isn’t enough and you need more.

A recent poll found that 53% of women want more sex than their sexual partner provides. A condition called hypoactive sexual desire disorder (HSDD) is very common in women, occurring in around 43% of women. Unfortunately, there are very few medications for women to correct this. Sex drive does encompass a variety of actions and concepts. For men, usually they just need their willing partner. However, erectile dysfunction occurs in 30 million men.

For women, it can become a lot more complicated.  Women’s needs may include more romance and caring. They may nee more empathy, sincerity, commitment, and honesty. They may need to be attracted to her sexual partner mentally or physically and have created a bond with the partner of trust and reliability. Plus, they need a willing partner too. Everyone is different.

Medical conditions can also alter libido. Diabetes many times has neurological issues that make it difficult for the man to become erect and also decreases his libido. Women diabetics may also suffer. Heart disease, autoimmune diseases and other debilitating diseases can zap one of their energy, resulting in low sex drive and performance.

If her/his emotional needs are adequately fulfilled, hormone levels are boosted to optimal levels, and medical conditions are adequately resolved, if there still is a need for further sexual enhancements, certain peptides may fill this need.

Barbie Doll Peptide

One peptide that improves libido is bromelanotide, or PT-141. It works centrally on the brain to improve libido and sexual performance. This peptide does other things too. It also stimulates the pigments in our skin, called melanocytes, which results in you getting a bit of a tan when used regularly. In addition, it can decrease your appetite, so you could lose weight.

Thus, this is called the Barbie Doll Peptide: it gives you a tan, helps you lose weight, and stimulates your sex drive all at the same time. However, it not only works in women, it also works similarly in men and not only increases a man’s sex drive, it can also improve penile erections.

PT-141 works by binding to receptors in the brain called melanocortin 3 and 4. It then activates these receptors resulting in increased sexual desire and the arousal response.[1] Studies on women who had received PT-141 showed the women’s sexual drive was significantly increase and they were more satisfied with sex within 24 hours after the treatment, compared to those taking placebo.[2] Men also had improved libido plus erections were better; many times ED resolves when PT-141 is used.

Of note, PT-141 does not work on the vascular system as do Viagra and the other PDE5 inhibitors. It works directly on the areas of the brain that increase sexual desire via the nervous system.[3] Thus, it is very useful in women and studies have shown a marked increase in sexually satisfying experiences with it.[4] Men with erectile dysfunction also benefit with PT-141 providing increased erectile activity.[5] Although it is not FDA approved, application has been made.

Another peptide that works in a similar fashion to PT-141 is Melanotan II. It has been shown to increase sexual libido and performance, increases pigmentation of the skin, and decreases appetite similar to PT-141 for they both work on the same area in the brain that enhances libido, both can increase libido, and both have similar side effects. If one doesn’t work, one can always try the other peptide, since each has a slightly different effect on each individual.

Side Effects from PT-141

Generally, studies have demonstrated very little problems from use of PT-141 and it has been found to be safe and well-tolerated. However, there are a few potential side effects that occasionally occur that you need to be aware of.

PT-141 may raise blood pressure, and this problem is rarely seen using the injections. It is common with the nasal sprays, so this route is not recommended. In fact, injections are the only form of PT-141 that is FDA approved, and we prefer to use the injected form to reduce the risk of this potential side effect. In addition, using the injection method is safe to use with alcohol.

In men, PT-141 is very useful particularly for those men who do not respond well to Viagra or similar drugs that correct erectile dysfunction. Sexual satisfaction is significantly increased in men when this peptide is used. Studies have shown significantly greater sexual satisfaction in the group of men using PT-141 compared to those receiving placebo.

Other side effects may include nausea, muscle aches, flushing or headaches. However, for the most part, PT-141 is very well tolerated. In addition, it’s dosage can be variable: it can be using regularly every day, every other day, or as need. Thus, use of the peptide can be tailored to the person’s individual needs and schedule.

In men, the sex enhancing peptides may rarely result in prolonged erections. If this lasts for several hours (called priapism), this could result in injury to the penis, a visit to the ER, and further injury when they try to fix it. For sure, do not use these with Viagra or other PDE5 inhibitors for the chance of getting this problem is increased when the combo is used.

The downside of using the peptides is that their onset of actions is variable depending on the person. In some people, they may be ready for sex in 30 minutes, while in others it may take 6 to 12 hours before it “kicks in”. In addition, it must be injected for best results and it must be refrigerated until used.  Fortunately, the injection is with using a very tiny needle, so the fear of injection goes away rather quickly in most people, especially when they feel the great effects.

Dosage: Normally 0.15 to 0.2 cc of the peptide is administered SQ (in the belly) 2 to 6 hours prior to the sexual event. Some people prefer to take it once or twice daily for maintenance. Results are variable so each individual person may design his/her own dosage schedule according to how they react to it.

Summary:

Low libido (sexual desire) is a big problem, especially with a woman but some men suffer from this, and some men suffer from erectile dysfunction. There are two peptides that work well for these problems and have shown very significant increases in libido, sexual satisfaction, and correction of ED. Time of onset is variable as is dosage, but effects are very significant for those who need a boost in their sexual life and want to enhance their mojo.

References:

[1] Gelez, H.; Shadiack, A. M.; JG, P. Brain Activation Following Peripheral Administration of the Melanocortin Agonist PT-141. Program No. 418.16. 2005.

[2] Diamond LE. Et al. n Effect on the Subjective Sexual Response in Premenopausal Women with Sexual Arousal Disorder by Bremelanotide (PT‐141), a Melanocortin Receptor Agonist. The Journ of Sexual Med. 3(4) June 2006. doi.org/10.1111/j.1743-6109.2006.00268.x

[3] Shadiack AM, et al. Melanocortins in the Treatment of Male and Female Sexual Dysfunction. Current Topics in Medicinal Chem. 7(11)2007:1137-1144.

[4] Clayton AH. Et al. Bremelanotide for Female Sexual Dysfunctions in Premenopausal Women: A Randomized, Placebo-Controlled Dose-Finding Trial. Women’s Health. June 2016. https://doi.org/10.2217/whe-2016-0018

[5] Molinoff PB, et al. PT‐141: A Melanocortin Agonist for the Treatment of Sexual Dysfunction. Ann NY Acad of Sciences. 994(1) Jan 2006. doi.org/10.1111/j.1749-6632.2003.tb03167.x