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

Robert True

Peptides Part 2: Anti-Aging, Anti-Inflammation, Autoimmune Disease and Energy Production

From the first part on Peptides we learned that Peptides are sequences of amino acids that have amazing functions that can improve your health, your muscles, your immune status, your energy level, and much more. Some peptides can act as anti-aging agents, particularly by boosting levels of growth hormone that can strengthen your body, improve your minds, and help you lose weight. They may also decrease the effects of aging on your body to decrease age-related diseases.

In this second part of this series, we will discuss the peptides that can decrease inflammation, which is the root cause of chronic medical illnesses. In addition, poor energy production from aging mitochondria contribute this, and there is a peptide that will help this too.

Senolytic Peptides: Remove Old Dysfunctional “Old” Cells and Decrease Inflammation

As you age, cells within you become old and need to be removed to allow new cells to come from your stem cell pool and replace them with new cells. However, sometimes these old cells don’t go away. They are not functioning well, but persist, and therefore are called senescent cells. Unfortunately, these senescent cells induce an inflammatory response that tries to get rid of them, but it can’t, so inflammation sets in and can cause problems.

If these old cells linger, they can increase inflammation in their area which can cause further damage to the tissues and more bad aging. If we can improve the efficiency of removal or repair of these senescent cells, we may decrease the age-related inflammatory problems that they can do. This damage may contribute to the age-related decline we see in multiple organ systems as we age.

The Thymus and Thymosin Peptides

Fortunately, we have peptides that can remove these senescent cells. Called Thymosin Alpha-1 and Thymosin Beta 4, these peptides actually are found in the thymus gland. This gland is present in the upper middle part of your chest. When you’re young it is quite large and functioning at its max. Unfortunately, as you age, its size shrinks significantly such that when you’re older you hardly can even see it.

The function of the thymus gland is to mature T-cells that were made in your bone marrow. T-cells are immune cells that fight off foreign cells that are in your body, such as bacteria, viruses, and even newly formed cancer cells in your tissues. They also get rid of old senescent cells. They are your body’s natural way to control senescence.

Unfortunately, as you age, the function of these is compromised, just like the thymus gland shrinks as you grow older. However, by giving Thymosin Allpha-1 or Thymosin Beta 4, these functions are boosted resulting in an improved immune response.

Thymosin Alpha-1 is and immune modulator and stimulates your immunity in multiple ways. One way is to repair or remove senescent cells so new regenerated cells can grow and replace them, resulting in giving you healthier tissue.

This improved immune response also fights off inflammatory conditions, such as in autoimmune diseases.[1] These include rheumatoid arthritis, lupus, and muscular sclerosis (MS).

Thymosin Beta 4 directly matures stem cells with regeneration and repair of injuries. It has been used in multiple situations including dermal wounds, repair of ligament damage, repair of the heart following myocardial infarction, and healing of the brain following stroke, trauma and neurological disease. It may also be helpful for repair of spinal cord, bone and ligament damage, as well as counteract the effects of aging and viral infections. [2]

Thymosin Beta 4 can also reduce senescent cells, particularly those involving the endothelium of your arteries to improve their health. Preserving the health of your arteries improves blood flow to all organs, improving overall health.

It also reduces inflammation to improve healing. It promotes formation of blood vessels (angiogenesis) to improve blood supply to the injured tissues so they heal better. They stimulate stem cells to replace old senescent cells, reduce scar formation, and multiple other actions. Together these actions promote tissue repair and rejuvenation, needed actions to keep our bodies in good shape.

Autoimmune Problems

Some people develop a problem called autoimmune disease as they get older. These are diseases such as lupus, muscular sclerosis (MS), rheumatoid arthritis, cystic fibrosis, asthma, atopic dermatitis, and others. These are caused by excessive inflammation within their body’s that is directed against itself and can destroy or damage internal tissues. Taking the Thymosin peptides has been shown to be very helpful and beneficial in these diseases.

By improving the immune response, particularly T-cells that “clean up” the mess from inflammation, the problems with these disorders tend to resolve or get better over time. These peptides also enhance T-regulatory cell (T-reg cells) that are important for immune tolerance. They promote NK cells, that are “Killer” cells that attach unwanted cells and help remove them from the area. They also enhance production of many different anti-inflammatory compounds, called cytokines, to “cool-down” the inflammation and decrease pain.

Thymosin beta-4 has even further actions for wound healing, cardia and neuroprotection. It is especially helpful when high levels of inflammatory states and cancer in an effort to reverse the process or the culprit that is causing the problem. It is the most abundant thymosin from the thymus when it is working properly.

Dosage: Thymosin Alpha 1 dose is between 300 to 600 mcg SQ given daily or in divided doses. Thymosin beta-4 dose is 100-300 mcg SQ daily or twice a day. Thymosin beta-4 should be limited to 3-month cycles that can be repeated twice a year.

Energy Peptide: MOTS-c

As you age, mitochondrial damage occurs due to formation of free radicals (ROS) from normal functions of the mitochondria to produce energy (ATP) for the cell. MOTS-c is a mitochondrial peptide that protects the mitochondria from this damage, thus playing a role in continuing function of the mitochondria. This may ultimately correlate with extended longevity.[3]

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 and helping patients lose weight.[4] This may improve processes such as aging, inflammation, and stress resistance. MOTS-c is actually produced via the mitochondria’s own DNA to protect the mitochondria from degradation.

Dosage: 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.

Summary:

Thymosin’s are peptides that are produced naturally by the Thymus gland that help mature T-cells that are made in the bone marrow, plus enhance other aspects of the immune process. Because the Thymus shrinks with age, these functions decrease with age but can be boosted back up with administration of these peptides. They help in many autoimmune diseases and are anti-aging too.

By giving people MOTS-c peptide, your ability to produce energy is enhanced. With 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 could help protect you from these conditions while improving your energy levels.

References:

[1] Pica f. et al. Serum thymosin α 1 levels in patients with chronic inflammatory autoimmune diseases. Clinical & Experimental Immunology. 186(1). 28 June 20116. https://doi.org/10.1111/cei.12833

[2] Goldstein, A. L., & Kleinman, H. K. (2015). Advances in the basic and clinical applications of thymosin β 4. Expert Opinion on Biological Therapy, 15(sup1), 139–145

[3] 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

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

Robert True

Peptides, Part 1: Boost Your Body Fitness with Growth Hormone Physiologically

Peptides are sequences of amino acids that have amazing properties that can improve your health, your muscles, your immune status, your energy level, and much more. They have been around for years but only over the last few years has their benefits really been appreciated.[1] Now you can enjoy these benefits too if you embrace their powers.

Peptides are essentially signaling proteins that tell particular cells in parts of your body to do certain functions. Each peptide can exert a specific signal to different cells in your body which results in a desired action for improving your life. They may correct the underlying mechanism of action of many different disease states and can boost your quality of life too. Peptides build strength and improve weakness as we grow older.

The Aging Process

You all know that you’re going to grow older, which is good because the alternative isn’t so good. However, you want to grow older with good health, with a fit body, and with a clear mind that still remembers stuff. To age well, you need to do maintenance and take care of your body. Peptides may be a method for you to assist you in this process.

Before we go further, let’s discuss what happens when you age. As you get older, your body tends to go into a catabolic (breaking down) state instead of an anabolic (building up) state. You see a decrease in energy, which is from dysfunction of the powerhouses of your cells, the mitochondria. This dysfunction is due to increases in free radical formation within the mitochondria as they produce energy, also called reactive oxygen species (ROS).

You may see yourself gaining weight that is mostly fat and not muscle. You may also see a decrease in muscle mass, and when this becomes really bad it is called sarcopenia, and you become frail. If the mental function is not maintained adequately you will see a decline in your cognitive functions and memory becomes poor. You start to have that foggy brain problem.

In addition, your ability to fight off foreign invaders tends to decline and be less efficient, which is your immune response. This decrease in immune response results in poor ability to fight off infections and to get rid of bad dysfunctional cells that occur as your age, including spontaneous mutations of cells that could become cancer cells. The result is an overaggressive response by your immune cells with resultant formation of inflammation, which can then damage surrounding cells and tissues. The result is anatomic changes and dysfunction of the tissues that we see as we age; i.e. those aches and pains we notice as we get older.

Boost Your Growth Hormone (GH) Status Safely

As you age, your levels of growth hormone decline so that by age 80 you hardly have any HGH in your body. This results in much of the decline in your body as discussed above. With less GH you see decreased energy production, decreased muscle mass, increased fat mass, declining health and frailty. Many of these changes can be countered with hormone therapy, such as estrogen and testosterone, which we recommend that almost everyone should be taking if they can to keep their hormone levels optimized.

However, to boost this even more, an added hormone that can help prevent or reverse these chances is growth hormone. The safest and most effective way to boost your GH level is by using peptide therapy to stimulate your pituitary to secrete higher levels of growth hormone in a more natural fashion as you age. Combined with the other hormones, the result is increased lean body mass (muscles), decreased fat mass, which can help you lose weight, boosted energy production and a clearer mind,[2] a better memory,[3] and you feel great.

You may have heard of people using HGH (Human Growth Hormone) as an anti-aging regimen. However, you have probably also heard that it is very expensive, has lots of side effects, but does bulk you up. Unfortunately, actual growth hormone injections have turned out to not be the best therapy for anti-aging and may even do the opposite.[4] Thus, we do not recommend that you use human growth hormone, also called HGH, due to the many problems associated with it.

If excess amounts of GH are present, such as when you give yourself HGH shots, anti-aging benefits go away and the opposite may happen, as seen in genetically abnormal people who have excess GH present, called acromegaly. But when secreted in physiologic amounts, anti-aging levels are achieved, and this can be accomplished with use of peptides.

Certain peptides are a new option for boosting GH levels safely that can help you age with a better body and mind. They can give you anti-aging benefits. They are also less expensive. Plus, they allow your HGH to come from your own pituitary gland in a physiologic manner. There are several peptides that do this, including CJC-1295, Ipamorelin and Tesamorelin.

Side effects from doing GH are usually minimal and may include swelling of your joints. This is common with HGH injections, but not with the peptide injections because you’re just letting your pituitary do its job and secrete the right amount of GH in a physiologic manner. This means the pituitary secretes GH in a pulsed fashion, which is the natural way the pituitary works. Stimulating the pituitary to do this in its physiologic pulsed fashion is what controls the levels and prevents excess GH to be secreted. That’s what the peptides do.[5] You just want levels to replenish the gradual decline that you see as you age, not excessive amount.

Maintaining these levels of GH as you age can result in essentially improving the efficiency of every cell in your body. The result you see is you have more energy, develop more muscles, lose fat weight, and improve your immune status. Plus, you could potentially not only increase your quality of life, but also your lifespan, i.e. anti-aging.

Enhance Energy and Well-Being

When you have adequate levels of GH present, you essentially improve the efficiency and function of every cell in your body. Your body’s cells use less oxygen for exertion and there is less production of ROS (reactive oxygen species), which means less damage to cellular structures, such as mitochondria and DNA. Consequently, you see improved mitochondrial function and, as you recall, mitochondria are the powerhouses for every cell in your body. The more mitochondria you have and the more efficient they function; the more ATP is produced and the better energy you have.

In addition, by improving mitochondrial function, your heart pumps better, your muscles move with better endurance and strength, and you are able to build your muscles up like you did when you were younger. One of the obvious changes that is observed when you take these peptides is an increase in muscle mass and a decrease in fat mass, if you also exercise your muscles. In addition, with better energy your brain cells function optimally.

All these actions can result in improved quality of life and well-being. In addition, by maintaining the health of every cell, you generally feel more energy, you lose excess weight and you sleep better too.[6]

Decreasing Inflammation Results in Less Chronic Medical Problems

Inflammation is the root cause of most chronic medical diseases. No one wants to develop heart disease, Alzheimer’s disease or cancers. These all may be helped when the efficiency of the cells is improved. Increasing HGH through certain peptides may improve endothelial function and thus improve heart disease,[7] the number one killer of people.

Certain peptides have been shown to decrease hypertension, dilate blood vessels through NO production, improve cholesterol levels, and reduce intimal artery thickness,[8] reduce ROS, reduce inflammation, all of which reduces risk of cardiovascular disease. Improving the health of the lining of arteries, called the endothelium, is one of the most important actions you can do to improve your total body health. The multiple actions of GH via peptide stimulation can decrease cardiovascular disease.[9]

Intimal artery thickness is a measure of the thickness of the endothelium usually measured at the carotid arteries. If excessively thick, this correlates with increased cardiovascular disease. The thickening usually suggests the presence of plaques within the endothelial walls. If unstable, these plaques could rupture resulting in a blockage. In the heart the blockage results in a heart attack. If in the brain, the blockage results in a stroke. Neither one is a good option, so let’s try to prevent them with GH, because we can.

Brain cells have more energy too. This may translate to less chronic medical problems such as dementia and Alzheimer’s disease. One of the changes one sees with Alzheimer’s disease is a decrease in energy production from mitochondrial damage within the brain cells resulting in less ATP produced. Physiologic GH secretion may therefore improve this and potentially decrease your risk of developing dementias. Plus, as discussed, it can help prevent the cells from becoming senescent, rejuvenating brain function.

Alzheimer’s disease not only has decreased energy production from mitochondrial damage, but another hallmark sign is Beta-amyloid deposited on the neurons. This change starts with increased inflammation in the brain. It so happens that GH in the right amounts via stimulation by the peptides can potentially prevent this inflammation[10] and the Beta-amyloid deposition, allowing the neurons to continue to function in a more normal fashion.[11]

Decreasing inflammation may also decrease cancer risks.[12] Peptides seem to decrease development of cancers by decreasing formation of blood vessels to the cancers (angiogenesis), inhibiting transcription of genes that can cause proliferation of the cancers, and make the cancer cells die from internal cytotoxicity, also call apoptosis.[13] Less cancer risk equates to anti-aging too.

Dosage and Labs

We do not obtain growth hormone levels in the blood because it is expensive and difficult. Instead, we use IGFD-1 levels, which is produced by the liver as a direct result of GH secretion. This is therefore and indirect affect of the presence of GH but is used with good results. Deficiency of GH is variable between doctors, but generally if your IGF-1 levels are below 100 ng/ml you are most likely deficient in GH.

Dosage of CJC 1295 and CJC 1295/Ipamorelin is usually 0.1 cc (100 mcg) given as a subcutaneous injection (just under the skin in the fatty layer) with a very small needle for 5 days on and 2 days off. It should always be done at bedtime, before your sleep, for you make most of your GH when you sleep.

Conclusion

Not only can peptides increase your quality of life, they may also help protect you from developing the many chronic medical conditions that occurs with aging. When you get older HGH levels declines. Boosting HGH levels to higher levels in a physiologic manner with peptide releasing actions is a very good option for Anti-aging, a potential prevention strategy. Learn more about other peptides in subsequent parts of our Peptides series.

References:

[1] Henninot A, et al. The Current State of Peptide Drug Discovery: Back to the Future? J. Med. Chem. 2018, 61, 4, 1382-1414. July 24, 2017. https://doi.org/10.1021/acs.jmedchem.7b00318

[2] Aleman A, et al, Insulin-Like Growth Factor-I and Cognitive Function in Healthy Older Men, The Journal of Clinical Endocrinology & Metabolism, 84(2), 1 February 1999: 471–475, https://doi.org/10.1210/jcem.84.2.5455

[3] Devesa, J., Núñez, I., Agra, C., Bejarano, A., & Devesa, P. Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Al

terations and Had an ApoE 4/3 Genotype. International Journal of Molecular Sciences, 19(8), 2294. doi.org/10.3390/ijms19082294

[4] Tran D, et al. Insulin‐like growth factor‐1 regulates the SIRT1‐p53 pathway in cellular senescence. Aging Cell. 13(4) April 2014. https://doi.org/10.1111/acel.12219

[5]

[6] Sigalos JT, Pastuszak AW. The Safety and Efficacy of Growth Hormone Secretagogues. Sex Med Rev. 2018;6(1):45–53. doi:10.1016/j.sxmr.2017.02.004

[7] Randeva HS. Et al. Growth Hormone Replacement Decreases Plasma Levels of Matrix Metalloproteinases (2 and 9) and Vascular Endothelial Growth Factor in Growth Hormone–Deficient Individuals. Circulation. 2004;109:2405–2410.doi.org/10.1161/01.CIR.0000129763.51060.77.

[8] Laitnen ML. et al. VEGF Gene Transfer Reduces Intimal Thickening via Increased Production of Nitric Oxide in Carotid Arteries. Hum Gene Ther. 9(`5). Mar 2008. doi.org/10.1089/hum.1997.8.15-1737

[9] Berlanga-Acosta J, et al. Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effect. Clin Med Insights: Cardiology. March 2, 2017, doi.org/10.1177/1179546817694558

[10] Labandeira-Garcia J, et al.  Front. Aging Neurosci., 03 November 2017. https://doi.org/10.3389/fnagi.2017.00365

[12] Cicero AFG, Gogacci F, Colletti A. Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review. Brit. J of Pharmacol. 174(11). https://doi.org/10.1111/bph.13608

[13] Atul Tyagi, Abhishek Tuknait, Priya Anand, Sudheer Gupta, Minakshi Sharma, Deepika Mathur, Anshika Joshi, Sandeep Singh, Ankur Gautam, Gajendra P.S. Raghava, CancerPPD: a database of anticancer peptides and proteins, Nucleic Acids Research, Volume 43, Issue D1, 28 January 2015, Pages D837–D843, https://doi.org/10.1093/nar/gku892

Robert True

Exosomes; New Treatments for Improved Health Part 2: What Exosomes Can Do for You

To review from Part 1 of this series, exosomes are nano particles that are signals to rejuvenate your cells. They improve mitochondrial function, help kick out Zombie cells, and decrease inflammation. They stimulate your natural stem cells to come alive and replace old cells in your organs, rejuvenating them and helping them function in a healthier and younger fashion.

Inflammation and Chronic Medical Problems

Excess inflammation has been blamed for the root cause of all chronic medical conditions that you may acquire as you age. These include heart disease, the number one cause of death, neurodegenerative diseases such as Alzheimer’s disease, arthritis and cancers. Reducing inflammation thus is a primary goal when it comes to helping you live longer and with better quality.

Exosomes reduce inflammation through many processes, as was discussed in Part 1. This reduction of inflammation can thus give exosomes the potential power to reduce your risk of suffering from heart disease, lung disease and cancers. Other potential benefits could include reduce risk of developing diabetes, cartilage damage, systemic diseases, soft tissue repair and neuro-inflammatory diseases such as Alzheimer’s disease.

These signaling molecules, when injected into your body, travel around your body like tiny ambulances, they find the troubled area, i.e. areas on inflammation, and fix it. The Fix is to calm the inflammation, stimulate the stem cells in the area to become active to form new tissue cells, and stimulate repair of the area. This type of upkeep helps keep your tissues healthier to function better and with less pain. Exosomes are becoming a great option as an anti-aging therapy.

In order for exosomes to work best, you must also embrace the right lifestyle. Thus, losing weight and maintaining the proper diet is important as is exercising regularly and maintaining proper hormone levels. But now you have this new potential treatment that can boost your life even more.

Increase Your Vascular Health

All your organs need oxygen and nutrients that are brought to them via your blood vessels and your heart, i.e. your cardiovascular system. Damage to the inside lining of your blood vessels can occur as you age. This lining, called endothelium, can get damaged due to high blood pressure or deposition of the small bad granules of cholesterol that can collect below the endothelial lining.

Your body tries to repair this by sending in immune cells to fix this damage. Unfortunately, if excess, the excess immune cells needed can result in inflammation, which may cause more damage. If this damage continues, narrowing of the arterial channel can occur with decreased blood supply to the organ. If an artery in the heart becomes excessively inflamed, it could rupture and cause a heart attack.

Heart disease has been associated with development of dementias, such as Alzheimer’s disease, and cancers.[1] All of them are associated with excess inflammation. Exosomes thus could potentially decrease your risk of developing these chronic conditions by decreasing inflammation and rejuvenating the cells within your vessels.[2] In turn this improved vascular health would benefit the brain to potentially decrease dementias, and to decrease risks of cancer formation.

Osteoarthritis: Joint Pain of Old Age

As you age, you may develop inflammation of your joints called osteoarthritis. This is a very painful and debilitating disease that may cause severe disability and disfigurement. Exosomes have been shown to calm down the immune system in your joints and decrease inflammation. This in turn results in pain relief.

However, as you recall exosomes also can stimulate stem cells to come alive, replace and rejuvenate the tissues of your body. Thus, exosomes may help your natural repair process get rid of damaged cells and to rejuvenate the injured tissue, making the repair process happen more efficiently.[3]

Remember that exosomes are signaling compounds. Thus, exosomes may help the rejuvenation by stimulating formation of new tissue in the joints, i.e. they awaken your natural stem cells that are still present in the area to function and start building new tissues/cells. These tissues could include the cartilage in your knees,[4] the ligaments that might have gotten injured, stretched, or torn; or tendons and muscles that may have been damaged from multiple reasons. Cartilage repair is very beneficial to improving joint health and exosomes may stimulate this repair and rejuvenation,[5] and thus have been shown to be beneficial for many orthopedic conditions.

Neurodegenerative Diseases: Alzheimer’s Disease and Parkinson’s Disease

An exciting potential application of exosomes is for calming down the inflammation that is the root cause of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Exosomes have been shown to decrease the levels of certain cytokines in the blood. It is thought that, because they are signaling molecules, they modulate microglial activation, which are the cells that become inflamed in these disorders.[6] They may also decrease the beta amyloid deposition that accumulates on neurons and is thought to be part of the pathologic process of Alzheimer’s disease.[7]

Because exosomes gravitate to, attach onto, and modulate inflamed tissues they are ideal carriers to not only calm the inflammation through their signaling mechanisms, but also to potentially carry other medicinal compounds to these areas that might help in the resolution of the pathologic changes that are characteristic of neurodegenerative diseases.[8] They bring a sense of hope to the future cure of these problems if they ultimately are shown to provide such amazing actions safely.[9]

Conclusion

Exosomes are a new promising signaling compounds that may decrease inflammatory conditions that cause age-related conditions within the body. Inflammation is the root cause of chronic medical disease, whether it be Alzheimer’s disease, heart disease, arthritis, or cancers. Exosomes have been used in neurodegenerative disorders and orthopedic disorders with good results. They may also be beneficial for others, but further studies need to be done to determine this.

 

Note: Exosomes are still in the early stages of development. They have not been evaluated by the FDA and therefore use of them are considered off-label. They have not been approved for the diagnosis, treatment, prevention, or cure for medical conditions.

[1][1] https://newsroom.heart.org/news/heart-disease-and-cancer-risk-may-be-linked

[2] Chang, Y.-H., Wu, K.-C., Harn, H.-J., Lin, S.-Z., & Ding, D.-C. (2018). Exosomes and Stem Cells in Degenerative Disease Diagnosis and Therapy. Cell Transplantation, 27(3), 349–363. https://doi.org/10.1177/0963689717723636

[3] Cosenza, S., Ruiz, M., Toupet, K. et al. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep 7, 16214 (2017) doi:10.1038/s41598-017-15376-8

[4] Wang, Y., Yu, D., Liu, Z. et al. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res Ther 8, 189 (2017) doi:10.1186/s13287-017-0632-0

[5] Toh WS, et al. MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment. Seminars in Cell & Develop Biology. 67, July 2017: 56-64. https://doi.org/10.1016/j.semcdb.2016.11.008

[6] Perets N, et al. Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders, Nano Lett. 2019, 19, 6, 3422-3431. doi.org/10.1021/acs.nanolett.8b04148

[7] Malm T, et al. Exosomes in Alzheimer’s disease. Neurochem Internat. July 2016. 97:193-199. https://doi.org/10.1016/j.neuint.2016.04.011

[8] Katsuda T, et al. The therapeutic potential of mesenchymal stem cell‐derived extracellular vesicles. Proteomics, 13:10-11. Jan 2013. doi.org/10.1002/pmic.201200373

[9] Jiang L. et al Exosomes in Pathogenesis, Diagnosis, and Treatment of Alzheimer’s Disease. Med Sci Monit 2019; 25:3329-3335. DOI: 10.12659/MSM.914027

Robert True

Exosomes: New Treatments for Improved Health Part 1: What are Exosomes

Exosomes are nano sized entities secreted by your stem cells that are signals for proper functions of the stem cells. They do a variety of actions for preserving the function of the stem cells that keep the stem cells functioning at their tip top health. Think of them as messengers that tell the stem cells to stay young and healthy.

Stem Cells, Mitochondria and Exosomes

The types of stem cells that make up the structural parts of your body are called mesenchymal stem cells, or MSC’s. Their function is regulated by the interaction between their DNA, which forms internal messengers called RNA, which forms the proteins that do all types of functions within your body. These proteins form enzymes that catalyze reactions needed for life, and they form the structures of your body.

One of the internal regulators of this entire process are exosomes, produced by the MSC’s. You could say they are the regulators that stimulate the process of life in the right directions. One of these processes is to regulate your mitochondria, the powerhouses in each of your cells. Without energy within every cell, we would not be able to live and do everything we do. You got to have energy being produced within you to function, in your brain for thought and your body for every other function you need to live.

Mitochondria, DNA and Aging

As you get older, your mitochondria tend to not work as well, as does about everything else in your body. But when mitochondria don’t work as well, the cell’s energy goes down, and you feel the effects by feeling more tired or fatigued. At the cellular level, you need your mitochondria to repair and protect your DNA from damage as it does its normal everyday actions to produce the proteins that we need for regulation of all our needs.

After all, anywhere you have activity, there is always wear and tear, and this is true concerning your DNA too. As you age, DNA is always under attack. It may mutate, code the proteins incorrectly, or be injured by many internal stresses, including damaging free electrons that occur from normal metabolism. This lowered mitochondrial function causes DNA to become damaged.

Damaged DNA could result in cell death, and your immune system must either repair the damage or clean up and get rid of these damaged cells. If too many cells become dysfunctional, a lot of clean-up is needed resulting in a lot of immune cells needed for the cleanup, and this excess results in inflammation. As the inflammation gets worse, it can cause further damage to the tissues, which you see in the many changes that occur in your body as you age, such as arthritis or even wrinkles on your face.

How Inflammation Damages Tissues

Think of your tissues as a beautiful town, full of activity and pretty streets. If invaders come into the city, your army (your immune cells) comes in to kick them out. As the battle escalates, your army need to use guns, then tanks, then bombs to win (inflammation). They kick the invaders out, but the collateral damage is tremendous. There’s lots of destruction of the buildings, streets and deaths of people occur within the city (the results of the inflammation). You rebuild your town, but it’s a long hard process (repair and rejuvenation).

The same type of scenario occurs all over your body but in a microscopic way. If it occurs in your powerhouses (your mitochondria) the result could be damage to them and poor output of you energy. Exosomes could help decrease damage to the mitochondria through a reduction of inflammation and stimulate the rejeneration to occur.

Exosomes may also signal the mitochondria to continue to work properly and keep producing the energy to ensure continued proper functioning within each cell. Thus, if you can slow the damage to your DNA, you can potentially slow down the aging process.

Stem Cells and Zombie Cells

Stem cells are in every part of your body. When activated, they replicate and replace old cells that have died. Unfortunately, another thing that happens as you age is your stem cell reservoir becomes harder to activate. Exosomes can activate these stem cells to rejuvenate your tissues by signaling the internal functions of the cells to come alive, replicate, and form new cells to replace old cells.

Exosomes also help rid your body of what we call Zombie cells. These are old cells that didn’t get the message that they have to go, and they just linger. When they accumulate, they steal the nutrients and natural rejuvenating signals from your cells that would ordinarily help them function in a more youthful fashion,  robbing you of your natural internal youthful rejuvenation process.

When this happens, your organs don’t function well, and you start to develop the many changes of the aging process. Your cartilage gets bad, hair doesn’t grow so well, and you are more likely to get disease of your heart, brain, lung, kidney, and other organs. In addition, these old cells (also called senescent cells) are more likely to develop into cancer cells. Thus, it is imperative that these old Zombie cells go away and allow new regenerated cells to replace them to keep your organs healthier.

Something that removes these cells or forces them to go into their natural cell death is called a senolytic. Exosomes act as senolytics and help remove these old cells while stimulating the formation of new cells from your stem cells. When the old cells die, this is called apoptosis, and this process is necessary to continually rejuvenate your cells, get rid of old ones and replace them with new youthful ones.

Summary

Thus, exosomes are compounds from stem cells that signal changes to your cells to keep their mitochondria functioning and maintain adequate energy to function properly. They also force old Zombie cells to go away and allow new cells to come alive from your natural stem cell reservoir that are everywhere in your body.

Exosomes decrease the inflammation that can occur due to normal wear and tear damage to the cells’ internal DNA and mitochondria. Decreasing inflammation within your body can thus get to the root cause of many age-related medical conditions, including heart disease, neurodegenerative disease, arthritis and cancers.

In Part 2 of this series on exosomes, we will discuss clinical applications of exosomes to help you live longer and with better quality of life.

Note: Exosomes are still in the early stages of development. They have not been evaluated by the FDA and therefore use of them are considered off-label. They have not been approved for the diagnosis, treatment, prevention, or cure for medical conditions.

Robert True

Alzheimer’s Disease Prevention Part 2: Reduce ROS – Lose Weight

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.

 

[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] 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

Alzheimer’s Disease Prevention: Part 3: Improve Heart Health to Improve Brain Health

To prevent Alzheimer’s disease, think about just improving the health of your heart and you’ll do the same for your brain health. Studies have shown that these two diseases correlate with each: the more you have a healthy heart, the less likely you’ll get Alzheimer’s disease. Those who practice a heart-healthy lifestyle starting in their 40’s is almost 70% less likely to develop Alzheimer’s disease.[1]

It’s about keeping your arteries healthy. Arteries feed every organ of your body, including your brain and the heart itself. These are your vascular system, and the heart is the pump that keeps the blood flowing through them. The combination of the two is your cardio (heart) vascular (arteries) system.

The arteries need to be wide open and their lumen should not be narrowed by cholesterol deposits or other obstruction. They need to be flexible, contracting and expanding whenever needed. In order to do this, your arteries are made up of a very complex system of endothelium (the lining of the arteries) and smooth muscles to all work in coordination to keep the blood flow good. Any blockage or disruption of this system can cause cardiovascular disease.

Improve the Endothelium

The endothelium is the inside lining of every one of your arteries. Think of it as a layer of tiny tiles laid side to side within the inside wall of every vessel in your body. Each thin cell (the tile) has lots of functions to make sure the endothelium works properly. They are not just static tiles on a curved wall; they must be functional units so the system works well.

The endothelial cells secrete a substance that acts like a thin lining on top of this layer of cells, which is called the glycocalyx. I have discussed the glycocalyx on another blog article [Link]. The endothelium with its thin glycocalyx do several things as outlined below.

Just think of all the things the endothelium must do to keep itself and your organs healthy. It must:

  1. Be able to expand and contract in conjunction with the muscles below it.
  2. Secrete a substance that lets the blood flow along it in a very slick manner
  3. Somehow repel the blood from scratching, tearing or damaging the endothelial cells themselves
  4. Secrete some substance that prevents clot formation
  5. Repair itself if a tear occurs
  6. Clean up and get rid of any old cells that have been damaged
  7. Prevent itself from attacks by viruses and bacteria.
  8. Replace old damaged cells with new cells
  9. Secrete some substances that tell the muscle around it to relax with the beating of the heart
  10. Tell the muscles when to contract to push the blood through between beats

This is most likely just a partial list, but it exemplifies the complex process that must occur to give you good arterial health. It’s not just about cholesterol levels. If you want the best heart health, you need to make every artery and capillary in your body as healthy as you can by making sure each of the above functions is working optimally. When you feed every organ well, each organ is better too. Thus, making your cardiovascular system healthy is one of the best ways to decrease your risk of developing all types of chronic medical illnesses, including dementias and even cancers.[2] The better your heart health, the less dementia and the less chance of developing cancers.

Is Cholesterol the Answer?

Doctors always make a big deal about keeping your cholesterol levels low. This stems from the Framingham studies that showed a correlation between high cholesterol levels and heart disease. But the story has gotten a lot more complicated. It’s not the total cholesterol that’s the problem, it’s the type of cholesterol.

To have the best endothelial health, you need to decrease the small “granules” of cholesterol. Those are the ones that can get stuck under the endothelial cells, collect, and cause a plaque formation over time. Then your immune system kicks in to get rid of these and clean up the mess. If inflammation occurs in these plaques, the plaques can become unstable, rupture, and then really cause a problem depending on where the plaque is. For instance, if in the heart the rupture could result in a heart attack.

Thus, making sure your cholesterol numbers are good is a very important idea. If they’re not, there are meds and supplements that you can take that will help this. Things like bergamot (from the bergamot fruit), polyphenols, and red rice yeast are supplements, the numerous statin medications are other options.

What Can You do to Improve Your Heart Health?

So your goal to improve your brain health and decrease your risk of developing Alzheimer’s disease is to improve your heart health. Actually, all the actions do both. We at TrueMD are dedicated to these goals. You can improve your health and wellness if are willing to let us help guide you to do the concepts that will help get you there.

Lifestyle changes and having an open mind to new concepts are important. If you want to know what to do, here are the concepts that you can do to improve your heart health and in turn improve your brain and your total body health:

  1. Lose weight and Eat Right: Maintaining a normal body weight is imperative. All studies confirm that the higher your BMI, the more likely inflammation gets worse in your body, which can then lead to formation of about any type of chronic medical illness you can think of.
    1. We recommend you get to a BMI of 20 to 25 and maintain it there if you can
    2. If you can’t, do a weight-loss program. Don’t delay! Remember the damage starts when you’re young so you must take care of your weight problem early for the best results
    3. The latest recommendations are a ketogenic type of Mediterranean diet, such as what we teach in our office. Studies confirm the beneficial effects of this type of diet
  2. Exercise your body and your mind:
    1. Physical exercise has been proven multiple multiple times to improve cardiovascular health. I don’t think we have to belabor this point.
    2. Also exercise your mind; keep you mind active with conversations, reading, learning new stuff or whatever. These also have been shown to reduce risk of dementias.
  3. Attack age inducers: Take supplements that help your endothelium
    1. Compounds that can improve the endothelial lining to repel blood, prevent clotting, make the lining slick, etc. Omega 3’s, vitamin E, are one type of supplement that may help.
    2. Substances that help in the dilation of the arteries to relax the muscles. They do this by increasing the production of Nitric Oxide (NO) that relaxes the smooth muscles in the walls of the arteries and makes them less “stiff”.
    3. Antioxidants and anti-inflammatory compounds that prevent damage to the endothelial cells plus prevent the inflammation that can occur once the vessels become inflamed due to internal injuries, e.g. from excess cholesterol damage.
    4. CoQ10 and other substances that improve mitochondrial function to improve the energy within the endothelial and muscle cells.
  4. Replenish low hormone levels
    1. Make sure you maintain good hormone levels. If these levels are low, replenish them to more youthful levels.
    2. Keeping your hormones at optimal levels when they get low (e.g. menopause and andropause) has been shown to improve your cardiovascular health and your brain health.
    3. When done correctly (and we usually recommend bioidentical hormone pellet therapy as the best option) you get the benefits while don’t have increased risks.
  5. Nourish your mind and soul
    1. Stress reduction – if you can’t reduce the stresses, at least manage your stresses
    2. Stay social with friends and family – known to keep your mind active and you happy
    3. Sleep adequately – get enough to replenish the neurotransmitters in your brain
    4. Stay sexually active, and this has shown to be beneficial for the former three items too.

Some natural food extracts, concentrated nutrients, that do a combination of many of these actions discussed on by blog include blueberry extract and Pomegranate Extract. Other supplements are resveratrol, curcumin, green tea, and quercetin.

 

 

[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] https://newsroom.heart.org/news/heart-disease-and-cancer-risk-may-be-linked

Robert True

Alzheimer’s disease: Amyloid or Cardiovascular Disease? Part 1: How do You Get It?

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 see clumps of a sticky substance called amyloid that appear to be stuck on the nerve cells in an irregular fashion. You also 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) 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 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.

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 Inflammatio

Your body was built to repair itself down to the micro level. If you cut yourself, your body repairs the cut. At the cellular level, if ROS damages your mitochondria and the surrounding parts of the cell, your bodies 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.

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

Be Smart, Exercise Your Heart At least Once a Week

Cardiovascular disease is the number one cause of death as we grow older. If you can reduce your risk of developing heart disease, would you do it?

Staying active and incorporating exercise into your lifestyle has been associated with reducing heart disease. However, many people can’t seem to find the time to do it. How about if you could exercise just once a week for improving your heart would you do it?

For best heart health, most authorities recommend that you exercise vigorously for 20 to 30 minutes a day for 4 to 5 times a week. Even more is okay and may be beneficial. If you can do this, definitely keep doing it. If you can exercise to meet these standards, you are improving the health of your heart, your brain, and essentially your total body health.

There are a plethora of studies support the concept that exercising regularly improves your health. But supposed you just don’t have that much time to exercise the recommended amount of exercise. There are studies that suggest that you can still receive the benefits from exercise by exercising much less, even once a week if you do it correctly: it must be done vigorously.

Can You Exercise At least Once a Week?

A recent study in the British journal of Sports Medicine in 2018 showed that running definitely decreases your risk of all-cause cardiovascular and cancer mortality.[1] They analyzed 14 studies and tracked the health of 232,149 people over time. Research was carried out all over the world, including Australia, Austria, Finland and Thailand. People were followed for up to 35 years.

They found that any amount of running at any pace appeared to lower the risk of death from all causes for both men and women by 27%. Cardiovascular disease death rate reduction was 30% and cancer death risk was lowered 23%, compared to not running.

What was so interesting about this study was that, when the data was analyzed, there was no significant dose-response difference. In other words, you could get similar results whether you ran weekly or daily, at a real fast pace or a moderate pace, and the total amount of running varied too, but any type still provided benefits.

Thus, can you imagine you running just once a week for less than 50 minutes at a speed of around 6 mph, and still get this benefit of a healthier heart and less cancer? Essentially this is what this study is concluding. According to this study, you can significantly lower your risk of death from all causes by doing whatever exercise activity you can do during the week, as long as you do it vigorously and for at least an hour a week.

What’s Your Situation?

You may have to wake up early, drive half hour or an hour to work every day of the week; drive back home at the end of the day for the same time, and when you arrive home you’re too tired to exercise. Weekends, however, may be your savior. Now, with the evidence from this study, you don’t have to feel guilty that you can only get your exercise activities for your health just during your weekends.

Although this study concentrated on running, you most likely can get the same benefits by doing other types of exercise. Supposing you may have a knee injury or other injury that prevents you from running.  Replace the running with riding a stationary bike or an elliptical, or swimming? Most likely you could receive similar benefits from these activities as you would from running.

Many people do brisk walking, which is around 2.5 to 4 mph. This is probably not vigorous enough. Most people don’t increase their heart rate activity adequately just doing this. But if that’s all you can do, modify it. Doing upper body exercise as the same time as lower body exercise has been shown to increase heart rate activity better than just walking briskly, so try that if you can’t jog or run due to an injury.

This study was an observational study only and therefore cause and effect cannot be established with such studies. But the point is that any type of vigorous exercise at least once a week is probably very beneficial for your help to decrease your risk of dying from heart disease and cancers.

Conclusion

The authors of this study concluded, “Increased rates of participation in running, regardless of its dose, would probably lead to substantial improvements in population health and longevity.” Any type of good physical most likely will significantly lower your risk of death from all causes.

Thus, if you are just a weekend warrior and strive to exercise at least during weekends when you have more time, realize that you’re still doing a good job of decreasing your risks of developing heart disease and cancers. So go for it!

 

[1] Pedisic Z, Shrestha N, Kovalchik S, et alIs running associated with a lower risk of all-cause, cardiovascular and cancer mortality, and is the more the better? A systematic review and meta-analysisBritish Journal of Sports Medicine Published Online First: 04 November 2019. doi: 10.1136/bjsports-2018-100493

Robert True

Blueberries, Anthocyanins and Your Health

Blue berries are great to improve your health. But have you ever wondered, “Why?” Most likely the answer is that blueberries contain an ingredient called anthocyanin, which is in the blue pigment that colors the blueberry that bluish-purple color. There is a great deal of research that support the health promoting qualities of blueberries.

The word anthocyanin comes from the Greek language: Anthos = flower and kyáneos = blue. It belongs to a family of compound called polyphenols, specifically the flavonoid group of polyphenols. You may have heard of polyphenols when it comes to the health promoting effects of olive oil, which are thought to come from the polyphenols in olive oil.

Anthocyanins are in a number of fruits, including grapes (and in wine), bilberries, blackberries, blackcurrants, elderberries, chokeberries, strawberries and (of course) blueberries. I love my berries, whether in the morning or in the afternoon. I mix them, add a little Splenda or Stevia, pour some half & half or cream over them, add a few pecans, and I get to enjoy a delicious health improving meal.

The Health Boosting Benefits of Anthocyanins

Anthocyanins are strong antioxidants and anti-inflammatory compounds. They have been shown to help protect the heart from developing heart disease, the brain from neurodegenerative diseases, and essentially all your body cells from the development of cancer growths.[1]

They enhance antioxidant defenses through multiple mechanisms. One is by increasing the activity of certain enzymes, SOD (superoxide dismutase) and glutathione peroxidase. These are probably two of the strongest enzymes that help protect cells from damage that can occur due to free radical formations during normal metabolism. This is considered antioxidant activity, and anthocyanins are strong antioxidants, which correlate with anti-aging results.

This includes protection from damage of mitochondria and DNA. Mitochondria are powerhouses for every cell, and protecting their health helps ensure good energy production within each cell. Protecting your DNA does a lot of things, not only does DNA create the reactions within each cell that keep it alive and active but protecting DNA from damage could also decrease mutations of the DNA, which could equate to potentially preventing some cancers from forming.

Protecting Your Heart and Blood Vessels

One common problem that results in the development of heart disease is clogging of the arteries and destruction of the arteries by oxidation of bad cholesterol. If you have more of the bad cholesterol, potentially more of this process occurs, accompanied by worse chance of you developing heart disease.

Human studies have confirmed the antioxidant actions of anthocyanins to reduce cardiovascular disease risks. In one study,[2] 120 patients with high lipids were given anthocyanin had a reduction in bad lipids and an increase in good lipids, equating to a potential decrease in risk of developing cardiovascular disease. Raising your HDL and lowering the LDL have been shown to be good strategies for reducing the risk of developing cardiovascular disease (CVD).[3]

Blood vessels must be healthy for adequate blood to flow freely within their lumens. We know that the inside linings of blood vessels, called the endothelium, is very important for maintaining this good blood flow. If this lining collects small areas of bad cholesterol underneath it, this could be a problem. Once these “plaques” develop, inflammation and scaring can occur resulting in atherosclerosis, otherwise called hardening of the arteries.

Along with this hardening is a “stiffness” that can occur along the arteries. To help prevent this, the endothelial cells produce a compound called nitric oxide (NO) which dilates the arteries and makes them less stiff for better blood flow. Anthocyanins have been shown to decrease formation of atherosclerosis in animal models partly by increasing the formation of nitric oxide in the endothelium.[4]

Anthocyanins Decrease Inflammation

Not only can anthocyanin relax and dilate the arterial walls to reduce blood pressure, they also can reduce inflammation that may be building up and damage the endothelium. Anthocyanins are polyphenols and are found in many colored vegetables and fruits, and have also been shown to decrease platelet aggregation, which also helps in the flow of blood through the vessels protecting the endothelium from damage.

Remember that inflammation is the root cause of chronic medical diseases. Inflammation can occur due to the deposition of the bad cholesterol under the endothelium. This deposition of the bad cholesterol (small particles) may progress resulting in a collection of this nasty stuff. Once accumulated, the body sends out messengers to clean it up and repair these collections. If excessive, the result is inflammation, which is not good. Inflammation of the material can liquify it and increase the risk of rupture of the vessel. If within the heart, the ruptured vessel may result in a blockage of flow of blood and a heart attack.

Blueberries Improve Blood Flow to the Brain

There has always been a connection between the brain and the heart: increasing heart diseases correlates with increasing neurological disease and damage. If blueberries can improve the blood flow to the heart, they can improve blood flow to the brain. There had been many animal studies that confirmed this correlation.

As we age, none of us want to suffer from degeneration of our brains (called neurodegenerative diseases) that could result in chronic diseases such as dementia, Alzheimer’s disease and Parkinson’s disease. Ingesting blueberry extracts may be beneficial in decreasing our risks of developing these brain problems.

An important human study has confirmed the connection between ingesting high amounts of blueberries, or their extracts, and improved brain health. Researchers in the UK gave concentrated blueberry extracts to a group of 26 participants for 12 weeks in a double-blind trial.[5] Not only did they evaluate the results using cognitive questions, but also by looking at MRI changes in brain activation as seen in the MRI’s of these individuals.

They found that those taking the blueberry extracts increased brain activity, had improved working memory and had improved brain perfusion and activation in brain areas associated with cognitive function. It is thought that this improvement may be due to improvement in the endothelium of the vessels that feed the brain, in addition to direct effects of the extracts on the brain.

Conclusion

In conclusion, anthocyanins are polyphenol compounds from blueberries, wine, and other pigmented fruits and vegetables. When ingested adequately, such as with concentrated extracts, they can decrease the bad cholesterol (LDL) while increasing the good cholesterol (HDL) These changes may help prevent dysfunction of the lining of the arteries (endothelium) in many ways, including by production of nitric oxide to dilate the vessels.

Concentrations of blueberries also may improve brain function in a similar way through through improved endothelial function. All these effects help improve the flow of blood (circulation) and thus decrease the risk of developing cardiovascular disease and neurodegenerative diseases.

 

References

[1] Pojer E. et al. The Case for Anthocyanin Consumption to Promote Human Health: A Review. Comprehensive Reviews in Food Science and Food Safety. Sept 2013. 12(5). doi.org/10.1111/1541-4337.12024

[2] Yu Q, et al. Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects. Amer. Journ. Clin. Nutrition. Sept 2009. 90(3):485-492. https://doi.org/10.3945/ajcn.2009.27814

[3] Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 2005; 96:1221–32. doi.org/10.1161/01.RES.0000170946.56981.5c

[4] Xu JW, Ikeda K, Yamori Y. Upregulation of endothelial nitric oxide synthase by cyanidin-3-glucoside, a typical anthocyanin pigment. Hypertension 2004; 44:217–22.

[5] Bowtell JL, Aboo-Bakkar Z, Conway ME, et al. Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation. Appl Physiol Nutr Metab. 2017;42(7):773-9. doi.org/10.1139/apnm-2016-0550