It is truly a privilege for us to address you on the occasion of a milestone that marks a before and after in the history of our institution: the opening of our new clinic in Barcelona, located at 8 Ferran Agulló Street.

This is not simply a new location; it is about bringing to the Catalan capital all the medical excellence, knowledge, and experience accumulated over more than thirteen years dedicated to Preventive and Healthy Aging Medicine. It is about continuing to accompany our clients on their journey toward active longevity, with more resources, more human talent, and more commitment than ever.

Neolife Team

Medicine for Healthy Aging and Proactive Prevention

Neolife was a pioneer in Spain in the clinical application of what was then called Anti-Aging Medicine, a term that, over time, has evolved and deepened into what we now know as comprehensive age management.

From the very beginning, when this approach was barely known, we were clear about our mission: to transform the way people understand and experience the passage of time.

We have witnessed the evolution of science, technology, and evidence, and we have always been on the front line, applying everything that truly makes a difference in health, well-being, and longevity.

Today, with over 13 years of experience, we not only maintain that pioneering spirit—we reinforce it with the opening of a center that represents the very best of who we are. In our Barcelona clinic, you will find a space designed not only with functionality and cutting-edge technology in mind but also with warmth and humanity. Because at Neolife, we believe that the medicine of the future cannot be separated from human excellence.

We are at the forefront of all advances in the field of healthy aging and proactive prevention. We incorporate into our protocols everything that solid scientific evidence has proven effective in improving our clients’ health, quality of life, and longevity. What is discussed at international conferences, published in PubMed articles, and implemented by leading institutions worldwide is already part of our daily practice.

If you have heard of advanced tests to measure biological age, gut microbiome analysis, genetic predisposition and pharmacogenetics studies, maximum effort tests with oxygen consumption measurement, body composition analysis using DXA, intravenous NAD+ protocols, cardiovascular risk testing with molecular biomarkers, vascular assessments, early cancer screening using liquid biopsies or next-generation imaging… all of this is already available to you at our Barcelona clinic.

And not just available—guided by the best-trained, most dedicated, and most discerning medical and technical team in the sector. Professionals who not only have scientific knowledge but who also understand people. Because as important as knowledge is the judgment with which it is applied, and the ability to listen, empathize, and support each client with humanity and commitment.

One of our founding principles has always been providing exquisite, personalized care. At Neolife, the client is not just a number or a clinical case. Every client is a person with a story, expectations, fears, and goals. That is why each assessment, each check-up, and each program we design is fully personalized. We create tailor-made solutions adapted to the specific circumstances of each client, and we do so with the utmost respect, confidentiality, and dedication.

We offer hormonal optimization programs tailored to every stage of life, for both men and women. Because hormonal balance is neither a luxury nor a trend—it is a key factor in cardiovascular, cognitive, sexual, emotional, and metabolic health. And we know how to address it through science and precision, with the safety provided by clinical experience and ongoing training.

We also help our clients regain control over their metabolism and body composition. Excess visceral fat or loss of muscle mass are not just aesthetic issues; they are risk factors for chronic diseases that can and should be reversed with the right approach.

We often receive clients with diffuse symptoms, unclear diagnoses, or conditions that have not found answers in traditional medicine. Chronic fatigue, insomnia, brain fog, sexual dysfunctions, muscle pain, or mood changes that do not respond to conventional treatments. Thanks to the knowledge we have developed in integrative medicine, hormonal optimization, and the physiology of aging, we can offer solutions where others cannot. Because we look beyond the obvious, and because we have diagnostic and therapeutic tools that conventional medicine has not yet embraced.

Our new clinic in Barcelona is not just a physical space: it is an extension of our philosophy, our commitment, and our passion for health. We want it to be a benchmark not only in Catalonia but throughout Europe for those seeking a type of medicine that does not settle for treating diseases but aspires to prevent them, to anticipate, and to optimize every stage of life.

We warmly invite you to visit us, to discover firsthand what a truly comprehensive and personalized approach to health means, and to become part of this community that refuses to age according to statistics but instead chooses to do so with quality, vitality, and purpose.

Thank you for your trust, for your time, and for walking alongside us on this journey toward active, conscious, and fulfilling longevity.

La entrada Neolife Clinic Opening in Barcelona se publicó primero en Neolife.

Exercises and training aimed at gaining muscle strength are more beneficial when it comes to combating aging, morbidity, and mortality.

Muscle strength has been defined as one of the main markers of health. Several studies have shown a devastating link between lack of strength and a worse aging process: higher levels of muscle strength make you live longer and better.

Dr. César Montiel – Neolife Medical Team

The evidence

A study published in the journal Circulation (1) analyzed over 123,000 people and followed them for an average of 34 years in order to quantify to what extent lifestyle habits in the U.S. population could strongly affect their health. The results showed that 5 lifestyle factors (no smoking, healthy weight, regular physical activity, healthy diet, and drinking alcohol in moderation) could prolong life expectancy at age 50 by 14 years for women and 12 years for men compared to those who did not adopt any healthy lifestyle habits.

For example, in the case of women who followed the 5 healthy lifestyle factors, the projected life expectancy at age 50 was an additional 43 years, i.e., to 93, while for those who did not adopt any of them it was 29 years, to 79. In the case of men with a healthy lifestyle, it was estimated that at age 50 they would live 37 years longer (up to age 87), compared to 25 years (up to age 75) for those who do not have a healthy lifestyle.

The COVID-19 pandemic led many countries to adopt a measure that many of us associated only with wartime: confinement. The reality check faced by most of us who were unable to leave our homes for almost 3 months, it was at this time was that our physical activity rates suddenly dropped dramatically. We went from being able to walk, run, and exercise freely to not being able to do so. This lack of movement made us realize that we had lost something that is part of the essence of being human: we are what we are because we move.  The result was that even those who were not so active before the pandemic had a compelling need to move.

In short, a sedentary lifestyle currently increases the risk of suffering up to 35 chronic diseases. Encouraging movement therefore, in addition to a healthy diet and a drastic reduction in smoking and alcohol consumption can help the population live longer, healthier lives.

Figure 1. Maintaining healthy lifestyle habits can extend life by more than 10 years. Li, Y., et al. Circulation,2018

What we can do

Another epidemiological study published in 2019 by one of the most prestigious medical journals, The Lancet (2), quantified the link between several risk factors and mortality in over 150,000 people from 21 different countries (including high, middle and low income countries), thus representing one of the most ambitious studies to date when it comes to analyzing the impact of lifestyle, education, or pollution on global health. Most of the data we currently have are derived from a combination of studies conducted over several time periods and with different methodologies, and few of them analyze low-income countries.

Figure 1. Link between risk factors and mortality (2). Yusuf,S., et al. The Lancet, 2020

The results showed that 75% of the cases of death were attributed to modifiable risk factors. Globally, the first factor is having a low level of education, the second is smoking, and the third is having low levels of strength (as measured by a manual grip test) (Figure 1). In other words, having a low level of strength is the third leading cause of mortality globally. The researchers quantified that those who are less strong have twice the risk of mortality than those with high levels of strength. For every 5 kg less hand strength, the risk of mortality increases by 16% (2).

These results are in line with a review with meta-analysis (3) that studied nearly two million people and found that having higher levels of strength was associated with a 40% reduction in mortality risk in women and a 31% reduction in men (Figure 2).

If we analyze the data obtained from the Lancet study and many others that are published every day, we can see how lifestyle habits determine an individual’s health condition. Although it is quite obvious, it seems that studies are needed to certify something that is logical and common sense, i.e., if you move more, if you eat less and better, if you don’t smoke and don’t drink alcohol, your health improves.

In Spain, we have gone from having a life expectancy of 42 years in 1921 to 82 in 2015 (4, 5) (Figure 3). The population is aging and, as it ages, its strength and muscle mass decreases. This is inherent to the natural aging process, but the rate at which it does so may be slowed. In this regard, physical exercise, especially strength training, can prevent functional deterioration even in older people, attenuating the loss of muscle mass (4).

Figure 3. Evolution of life expectancy in Spain and the world.

In light of the compelling data presented here, it is necessary to implement measures aimed at stopping as soon as possible a problem that is on the rise: sedentary lifestyles and their link to the development of chronic diseases.

Of all the modifiable factors shown in all these studies, but especially in the Lancet study, most diseases may be prevented through policies that encourage higher levels of physical activity and a healthy diet. In the particular case of strength, the evidence is overwhelming. Having higher levels of muscle strength makes you live longer and better.

BIBLIOGRAPHY

(1) Yanping L, An P, D. WD, Xiaoran L, Klodian D, H. FO, et al. Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population. Circulation. 2018 Jul 24;138(4):345–55. 

(2) Yusuf S, Joseph P, Rangarajan S, Islam S, Mente A, Hystad P, et al. Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet 2020 Mar 7;395(10226):795–808. 

(3) Leong DP, Teo KK, Rangarajan S, Lopez-Jaramillo P, Avezum  Jr A, Orlandini A, et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. Lancet. 2015 Jul 18;386(9990):266–73. 

(4) García-Hermoso A, Cavero-Redondo I, Ramírez-Vélez R, Ruiz JR, Ortega FB, Lee D-C, et al. Muscular Strength as a Predictor of All-Cause Mortality in an Apparently Healthy Population: A Systematic Review and Meta-Analysis of Data From Approximately 2 Million Men and Women. Arch Phys Med Rehabil. 2018;99(10):2100-2113.e5.

(5) Valenzuela PL, Castillo-García A, Morales JS, Izquierdo M, Serra-Rexach JA, Santos-Lozano A, et al. Physical Exercise in the Oldest Old. Comprehensive Physiology. 2019. p. 1281–304. 

(6) Hoffmann C, Weigert C. Skeletal Muscle as an Endocrine Organ: The Role of Myokines in Exercise Adaptations. Cold Spring Harb Perspect Med. 2017 Nov;7(11). 

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The energy and nutrients we obtain through food play an important role in the development and preservation of the immune system.

The nutritional approach to immune disorders should aim to maintain an optimal nutritional status, prevent deterioration during acute episodes, and improve it during symptom-free periods. The AESAN Scientific Committee Report shows that the immune system is strongly dependent on adequate and balanced nutrition.

Alejandro Monzó – Neolife Nutrition Unit

Relationship between specific nutrients and the pathogenesis, symptoms, and evolution of autoimmune diseases

The immune system consists of a network of specialized tissues, organs, cells, and chemicals that protect against infectious agents, toxins, cancer cells, and foreign tissues (1). There are many individual variations in immune functions caused by an individual’s genetic make up, nutritional status, stress levels, age, and lifestyle habits.

The immune system has several lines of defense. Early defense mechanisms aimed at combating and eliminating foreign elements involve physical, chemical, and biological factors, such as the skin barrier, mucous membranes, stomach pH, digestive enzymes, and others. When these mechanisms fail or are overloaded, innate and adaptive immunity take over (1, 2). Both interact with each other with the aim of preserving the body’s homeostasis. Innate immunity is the first to act, is natural and non-specific, does not require prior sensitization, is mediated by cells with phagocytic ability and (natural killer) cells and, by itself, allows the control of most of the pathogens that reach the body. Adaptive immunity is specific and has immunological memory when the body is exposed a second time to a given antigen, with priority participation of lymphocytes, and the antibodies and cytokines released by them.

In some people, the immune system is altered and finds it difficult to recognize its own cellular structures and tissues, so it initiates an attack against them. When this occurs, autoimmune diseases originate. Currently, over 80 diseases have been described and the autoimmune attack may be restricted to specific tissues or may be generalized, such as rheumatoid arthritis, lupus, type I diabetes, Hashimoto’s thyroiditis, Graves’s disease, celiac disease, Chron’s disease, multiple sclerosis, ulcerative colitis… (1, 2). In many cases, the reason why this happens is unknown; however, it is believed that the presence of some microorganisms, the ingestion of some drugs, toxins and/or certain chemical substances present in food may trigger this reaction, especially in the case of individuals who are nutritionally deficient or who have a greater genetic susceptibility to developing autoimmune disorders.

The development therefore, maintenance, and proper functioning of the immune system depends on adequate and balanced nutrition. According to scientific evidence, improper nutrition affects the innate and adaptive immune response, altering the response to infection, indirectly increasing the virulence of pathogens, and favoring the development of autoimmune diseases (Figure 1) (3). According to the previously mentioned AESAN (Spanish Agency for Food Safety and Nutrition), there are several reasons why the immune system depends on the availability of nutrients (1):

• The immune response is associated with the synthesis of new protein molecules and cell proliferation.
• Nutrients act as cofactors in many metabolic pathways that are critical to the maintenance of immune function. Moreover, they can regulate oxidative stress and cell membrane integrity.

Figure 1. Nutrients and their dietary sources are involved in the development and progression of rheumatoid arthritis (3).

The cells of the immune system rely heavily on their cell membrane function to perform operations such as cytokine and antibody secretion, antigen recognition, lymphocyte transformation, and contact-dependent lysis. The importance of lipids in maintaining membrane integrity suggests that these compounds may be critical nutrients in immune regulation and, in fact, fats have been shown to influence the severity of autoimmune diseases (4). A diet rich in long-chain omega-3 fatty acids is recommended in this type of disease because of its relationship with inflammatory processes, its anti-inflammatory role and positive correlation with the increase in white blood cell levels, the patient’s weight, and improvement of cardiovascular risk, and so they should provide 1-2% of the total energy provided by food (1, 2, 3).

In experimental animal models of autoimmune diseases, certain nutrients (polyunsaturated fatty acids, vitamins A, E, C, D, and B12) and probiotics produce significant clinical improvement and delay in disease onset. In patients with autoimmune diseases, some nutritional intervention studies suggest that various dietary components, especially omega-6, 3, EPA and DHA fatty acids, vitamin D, and selenium, as well as the administration of various probiotics in combination, may have an impact on patients’ clinical improvement (1).

As nutritional recommendations to optimize our immune system, we present the following foods and nutrients, which play an interesting role in the modulation of immune response (4, 6, 7):

• Vitamin A: beef liver and other organs, salmon, green leafy vegetables, colorful vegetables, egg yolk, dairy products, and fruits such as melon, mango, and watermelon.
• Vitamin C: citrus fruits, as well as fruits and vegetables in general, red and green peppers, tomatoes, broccoli, kiwi, and strawberries, among others.
• Vitamin D: Vitamin D deficiencies are associated with increased risk of infection and autoimmune diseases. It is found in fatty fish, fish liver oils, egg yolk, cheese, and mushrooms along with adequate sun exposure and/or supplementation.
• Selenium: participates in the production of important agents in immune and inflammatory response, in addition to improving the activity of natural killer cells. It is present in seafood, Brazil nuts, meats, eggs and other dairy products, bread, and cereals.
• Zinc: its deficiency increases susceptibility to infections; this nutrient is involved in multiple processes of the immune system. Oysters, red meats, seafood, legumes like chickpeas, and nuts are good sources.
• Healthy fatty acids: fish and seafood, nuts and seeds, plant oils and fortified foods like dairy.
• Interesting foods: broccoli, garlic, turmeric, ginger, green tea and mushrooms, kefir, and probiotic foods in general; the immune system benefits from their immunomodulatory functions, preventing inflammation.

While regular moderate physical activity facilitates body weight control, improves vascular health, and generally supports optimal immune function, intense exercise is consistently associated with short-term immunosuppression. This effect, which lasts 3-72h, is apparently aggravated by a relative depletion of carbohydrates and is mitigated by their consumption before or during exercise (4). And so, a study published in Frontiers in Immunology points out that proper nutrition together with regular moderate physical activity may prevent the risk of obesity and may improve immune function (Figure 2.) (5). It is worth noting that the immune system also benefits from periods of fasting, which promotes cell regeneration and reduces inflammation (6).

Figure 2. Link between nutritional status, immune metabolism, and immune function.

Finally, more and better quality studies are needed to better understand the impact of nutrition and nutrients on the pathogenesis, symptoms, and evolution of autoimmune diseases. In short, immunological disorders may be grouped into three major groups: allergies or states of hypersensitivity, states of immunodeficiency, and autoimmune diseases (1, 2). Here at Neolife, we prescribe a personalized nutrition plan based on the patient’s special needs. Following the latest advances in the scientific community, a diet can be an optimal tool, especially for the management of immune system disorders, which is why both medical and nutritional follow-up is essential in our clinic.

BIBLIOGRAPHY

(1) Report of the Scientific Committee of the Spanish Agency for Food Safety and Nutrition (AESAN) on the Role of Nutrition on Autoimmune Diseases. Scientific Committee Journal number 13. 2010. URL: https://fisiogenomica.com/assets/Blog/pdf/NUTRICION_ENFERMEDADES_AUTOINMUNES.pdf

(2) Plaza L. B. & Bermejo L., LM. (2017). “Nutrition and immune system disorders”. Nutr Hosp. Vol. 34(4): 68-71. URL: https://pubmed.ncbi.nlm.nih.gov/29156936/

(3) Gioia, C. et al. (2020). “Dietary habits and nutrition in rheumatoid arthritis: can diet influence disease development and clinical manifestations?. Nutrients.Vol. 12(5): 1456. URL: https://pubmed.ncbi.nlm.nih.gov/32443535/

(4) David L. Katz et al. Nutrición Médica 3ª Edición. Wolters Kluwer. 2015.

(5) Alwarawrah, Y. (2018). “Changes in nutritional status impact immune cell metabolism and function”. Front Immunol. Vol. 9: 1055. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968375/

(6) Vázquez, M. (2018). “Fortalece tu sistema inmune: mejores defensas = menos enfermedad” [Strengthen your immune system: better defenses = less disease]. Fitness Revolucionario. URL: https://www.fitnessrevolucionario.com/2018/05/26/como-fortalecer-sistema-inmune/

(7) National Institutes of Health. U.S. Department of health & human services. Dietary Supplement fact sheets. URL: https://ods.od.nih.gov/factsheets/list-all/

La entrada Nutrition and Immune System Disorders se publicó primero en Neolife.

The importance of maintaining optimal vitamin D levels after menopause

The decrease in female sex hormones causes fragility and loss of bone mass, which increases the risk of developing osteoporosis and fractures, a common occurrence in women over 50 years of age. However, let’s look at how we can minimize this impact on women’s bone health.

Dr. César Montiel – Neolife Medical Team

Menopause is a vulnerable stage, from a nutritional point of view, because energy expenditure decreases (due to changes in body composition and decreased activity), while the needs for some nutrients such as vitamin D increase (1, 2). Loss of ovarian function has a profound impact on female bone health. The decrease in bone mineral density accelerates in the year prior to the last menstrual period and in the following two years (5). Although the etiology of osteoporosis is multifactorial, vitamin D intake, from the diet and from supplements, appears to have a key impact on the maintenance of bone mineral density, prevention of fractures and falls (3-4).

Vitamin D plays a central role in calcium metabolism, so adequate intake, either through the diet or by cutaneous synthesis in response to sunlight, is essential for lifelong health. Parathyroid hormone or parathormone (PTH) regulates the production of 1,25 dihydroxyvitamin D and the formation of the active form of vitamin D necessary for calcium homeostasis. Chronic vitamin D deficiency leads to secondary hyperparathyroidism with higher bone turnover, progressive bone loss, and higher risk of fracture due fragile bones (5, 6).

The prevalence of vitamin D deficiency in the general population and especially in post-menopausal women is significant and is currently considered an important public health problem. This deficiency may have key consequences not only for bone health, but may possibly play a role in autoimmune, neoplastic, infectious, and cardiovascular diseases (6-7).

From a metabolic point of view, modern life has supposed for women, an increase in the prevalence of diseases such as obesity, insulin resistance, and diabetes, mediated by an increase in the amount of visceral fat. High-calorie diets, sedentary lifestyles, and all the unhealthy lifestyle habits of our urban life have contributed to this increase in pathologies that in the long run dramatically increase the risk of suffering a cardiovascular event.

In urban areas, 50% of women over 50 years of age suffer from this metabolic syndrome. This means that half of all women suffer from excess visceral fat at the abdominal level.

Moreover, vitamin D deficiency is considered to be the most frequent medical problem worldwide, intensifying after menopause (65% of postmenopausal women have severe vitamin D deficiencies).

Recent studies (1, 2) link vitamin D deficiency to the appearance of chronic diseases like high blood pressure and type 2 diabetes, which exponentially increase patients’ vascular risk. On the opposite side of the spectrum, patients with high vitamin D levels have a rate of cardiovascular events that is up to 51% lower than the normal population’s.

A meta-analysis of more than 210,000 patients confirms a 20% higher risk of these cardiometabolic pathologies.

In January 2018, the journal Maturitas published a cohort study of 463 postmenopausal women, showing that those with low vitamin D levels had a higher risk of metabolic syndrome, hypertriglyceridemia, and low HDL cholesterol (good cholesterol) levels, and that this risk was higher than in the population with low vitamin D levels, i.e., in postmenopausal women the effect of low vitamin D levels was more acute.

These results are consistent with the conclusions obtained in previous research (3, 4), and even in the WHI, in 2002, a possible link between low vitamin D levels and the occurrence of cardiovascular events was already mentioned.
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In these studies, in general, it is observed in a linear and exponential manner that, as vitamin D levels decrease, the risk of the previously mentioned vascular risk factors increases independently.

There are multiple pathophysiological mechanisms that may explain this association. The most logical, and also the most scientifically based, is that vitamin D has a crucial influence both on insulin secretion by the beta cells of the pancreatic islets of Langerhans and on insulin sensitivity by receptors located in skeletal muscle cells and adipocytes. When the concentration of vitamin D decreases, these mechanisms are altered, leading to a lower production of insulin with greater resistance to its action in the periphery, which is what triggers the metabolic syndrome.

Vitamin D deficiency affects the ability of the pancreatic beta cell to convert pro-insulin to insulin. With respect to insulin sensitivity, vitamin D regulates calcium levels in the extracellular space of both skeletal muscle fiber and adipocytes, which facilitates insulin action at that level. Vitamin D deficiency increases resistance to insulin action.

In these studies, levels below 30ng/ml are considered vitamin D deficiency, and levels below 20ng/ml are considered severe deficiency. Levels above 30ng/ml are considered sufficient; however, numerous publications demonstrate the need to reach vitamin D concentrations of around 50-60ng/ml, to prevent the possibility of suffering any of the consequences of vitamin D deficiency.

At Neolife, as with the rest of the biomarkers we study in our patients, we treat our patients to achieve vitamin D levels in a range of excellence that decreases the possibility of the onset of metabolic diseases, thus preventing the possibility of cardiovascular events. Additionally, with a proper diet, regular physical exercise, and the necessary daily amount of calcium and vitamin D, we can minimize the impact of estrogen depletion on women’s bone health after menopause.

BIBLIOGRAPHY

(1) Navia B, Ortega RM. Ingestas recomendadas de energía y nutrientes [Recommended energy and nutrient intakes]. In: Nutriguía. Manual de  Nutrición Clínica en Atención Primaria. Chapter 1. Requejo AM, Ortega RM eds. Madrid: Editorial Complutense. 2006; 3-14.

(2) Riobó P. Mujer adulta y menopausia [The adult woman and menopause]. In: Nutrición en población femenina: Desde la infancia a la edad avanzada. Ortega RM, ed. Madrid: Ediciones Ergón. 2007; 93-100.       

(3) Lowe NM, Ellahi B, Bano Q, Bangash SA, Mitra SR, Zaman M. Dietary calcium intake, vitamin D status, and bone health in postmenopausal women in rural Pakistan. J Health Popul Nutr 2011; 29 (5): 465-70.

(4) Boucher BJ. The problems of vitamin d insufficiency in older people. Aging Dis. 2012; 3(4): 313- 29.

(5) Melton LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective. How many women have osteoporosis? J Bone Miner Res. 1992; 7:1005–10.

(6) Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, et al. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J ntern Med. 2006; 260(3):245-54.

(7) Ahmadieh H, Arabi A. Vitamins and bone health: beyond calcium and vitamin D. Nutr Rev 2011; 69 (10): 584-98.

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It is common to find that our patients don’t understand how they can present a lipid metabolism disorder, when previously these parameters were always under control.

Something we frequently see in menopause are disorders that affect lipid metabolism (higher triglycerides and LDL cholesterol, lower HDL cholesterol, etc.). Women must prepare themselves, consider treatments, and modify their lifestyles if they wish to maintain optimal health.

Dr. Celia Gonzalo Gleyzes – Neolife Medical Team

A brief review of what we call the Lipid Profile

• LDL cholesterol: its function is to transport cholesterol to the tissues. Additionally, it is found in cell membranes and can be converted into various metabolites, such as steroid hormones. The LDL fraction contributes to the formation of atheroma plaques in the arteries, making them more rigid and potentially obstructing them (atherosclerosis).
• HDL cholesterol: the HDL fraction prevents the accumulation of LDL cholesterol. HDL displaces free cholesterol from cells and other lipoproteins. This cholesterol is transported to the liver where it is excreted through the biliary tract. HDL lowers the levels of cholesterol accumulated in the endothelium (cell wall) of blood vessels, thus benefiting the cardiovascular system.
• Triglycerides: constitute a form of energy storage. They can accumulate in adipose tissue and other organs causing diseases (hepatic steatosis, pancreatitis…). We obtain energy from fat by converting triglycerides into free fatty acids, which are transported (bound to albumin) to different tissues where they are oxidized. Elevated blood triglyceride levels are associated with cardiovascular disease, type 2 diabetes mellitus, and atherosclerosis.

Estradiol (E2) and lipid metabolism disorders

During a woman’s fertile life, the average estradiol level is 100-250 pg/ml, but this drops after menopause to 10 pg/ml.

This is linked to most of the problems suffered during menopause: sleep disorders, mood disorders, vasomotor symptoms (hot flashes, sweating), urogenital atrophy, osteopenia, osteoporosis, psychiatric disorders, sexual dysfunction, skin problems, cardiovascular diseases, cancer, metabolic problems, and obesity.

Estradiol is synthesized through the “use” of LDL cholesterol. During menopause, this cholesterol is no longer “spent” in this way.

Experimental data have shown that estradiol plays an essential role in the beta-oxidation of fatty acids in mitochondria.

Estrogens have an inhibitory effect on adipogenic genes.

Estrogen receptors alpha (ERα) regulate body fat distribution, adipose tissue inflammation, and fibrosis.

A recent study shows that women who have received aromatase inhibitors (a treatment used in breast cancer that aims to lower estrogen levels) had a higher percentage of body fat and a higher insulin resistance than control cases.

Aging is associated with changes in body composition; in women this happens during menopause. This may be due to the loss of the protective effect of estrogens and a relative increase in the levels of circulating androgens. It is suggested that sex hormones may have an influence on lipid profile because estrogen receptors are expressed in visceral fat and subcutaneous adipocytes.

In menopause, HDL cholesterol decreases and LDL cholesterol increases. Research has shown that HDL3-C increases, but HDL-2C decreases by up to 25% (cardioprotective sub fraction). LDL cholesterol may increase by 39-49%.

During menopause, adipokine levels (molecules related to adipocytes, angiogenesis, hunger sensation, etc.) are altered.

Higher visceral fat is linked to higher lipolysis, which increases the flow of fatty acids to the liver, worsening hepatic insulin resistance.

Lower energy expenditure in menopause

The drop in estradiol lowers the expression of genes specialized in efficient energy expenditure, which implies a greater tendency to gain weight and develop metabolic diseases during menopause.

The loss of lean mass with age (3-8% every 10 years after age 30) causes the resting metabolic rate (the calories we expend at rest) to lower. Women present sarcopenia earlier than men.

If we combine these two factors with a decrease in physical activity (which may be due to menopausal discomfort such as joint pain, urinary incontinence, fatigue…) we obtain a lethal combination that may lead to obesity in a short time. (1)

What can Neolife offer?

• An initial assessment for the detection of problems: biomarkers (review of lipid levels), a “snapshot” of complete body composition by means of a DXA, or “Dual X-ray Absorptiometry”, a very precise test that will show us fat mass, lean mass, and visceral fat. We will find out if the arteries are already damaged (carotid ultrasound and calcium score).
• Review of hormonal status with indication for full bioidentical hormone replacement therapy when necessary (the importance of estradiol has been made clear).
• Review of dietary needs and goal-setting. Our goal is to help menopausal women lose weight and gain muscle mass (to avoid sarcopenic obesity) while they follow a complete diet rich in antioxidants. Additionally, dietary patterns that promote osteoporosis (acidification, excessive consumption of soft drinks and coffee, etc.) should be avoided.

The hypocaloric diet will be accompanied by NeoVitamin Plus and NeoMineral Plus to prevent deficiencies and complications.

• Sports assessment: it is preferable to adapt physical activity to each individual. We cannot combine menopause with a sedentary lifestyle, as it leads to diseases like obesity and cancer.
• Supplementation: it will not replace the Mediterranean diet, but it will complete it. We most certainly need Neovitamin D3 (cholecalciferol) and NeOmega 3.

Overweight and age increase our vitamin D requirements (a hormone that allows the absorption of calcium at the intestinal level but whose deficit may be associated with various pathologies such as cardiovascular disease, autoimmune diseases, high triglycerides, tuberculosis, psoriasis, etc.).

Omega-3 fatty acids have anti-inflammatory and cardioprotective effects and improve insulin sensitivity. A Brazilian study showed that supplementation with 900 mg of omega-3 per day in menopausal women improved BMI, waist circumference, blood pressure, triglycerides, IL-6, and insulin resistance.

• Medical supervision: the road to good health is paved with professionals who will customize guidelines and clarify concepts.

BIBLIOGRAPHY

(1) Ko SH, Kim HS. Menopause-Associated Lipid Metabolic Disorders and Foods Beneficial for Postmenopausal Women. Nutrients. 2020 Jan 13;12(1):202. doi: 10.3390/nu12010202. PMID: 31941004; PMCID: PMC7019719.

(2) https://pubmed.ncbi.nlm.nih.gov/31941004/

La entrada Lipid Metabolism Disorders in Menopause se publicó primero en Neolife.

Numerous factors, from changes in eating habits to antibiotic treatments, influence the delicate microbial balance and lead to dysbiosis.

Dysbiosis refers to an imbalance in the number or type of microbial colonies that have colonized humans. Evaluating the relationship between the intake of ultra-processed foods, the changes produced in the microbiota and the risk of diseases, such as irritable bowel syndrome, is an interesting new field of study.

Alejandro Monzó – Neolife Nutrition Unit

Also called dysbacteriosis, dysbiosis can affect digestion, nutrient absorption, vitamin production, and control of harmful microorganisms.

The term microbiota refers to the set of microorganisms (all bacteria, archaea, eukaryotes, and viruses) present in a given environment, such as the intestinal tract. Scientists define the term microbiome as the entire habitat, including microorganisms, their genes, and external environmental conditions (1).

Endogenous human microbial communities are involved in multiple metabolic, physiological, and immunological functions, which is why any alteration in the function and composition of the microbiome may pose significant health consequences (2). The main functional contributions attributed to the human microbiome are presented below:

• Maintenance of the skin and mucous barrier function
• Food digestion and nutrition
• Energy generation and vitamin production
• Metabolic regulation and control of fat storage
• Processing and detoxification of environmental chemicals
• Differentiation and maturation of the host mucosa and their immune system
• Development and regulation of immunity, helping to maintain the balance between proinflammatory and anti-inflammatory processes
• Prevention of invasion and growth of disease-promoting microorganisms
• Contribution to the development and maturation of the nervous system

The human microbiome is mainly defined by two types of bacteria, Firmicutes and Bacteroidetes, the latter accounting for 90% of the intestinal microbiota and, to a lesser extent, actinobacteria.

New studies show that dysbiosis has been associated with a number of gastrointestinal disorders, such as irritable bowel syndrome (IBS). Significant differences have been seen in the microbiota of IBS patients compared to healthy control subjects. Additionally, other research has identified a link between IBS and bacterial overpopulation through the use of breath testing (3).

An individual’s diet is one of the key modulators of gut microbiota composition that directly influences host health and biological processes, but also through metabolites derived from microbial fermentation of nutrients, specifically, short-chain fatty acids (2,3). In this regard, a new study published in the British Medical Journal shows that ultra-processed foods are associated with a higher risk of inflammatory bowel disease (4).

Ultra-processed foods include baked goods, sugary drinks and soft drinks, precooked foods, reconstituted meat and fish products, snacks, and all kinds of packaged foods, which often contain high levels of sugar, salt, additives, and unhealthy fats. These are packed with energy but provide insufficient amounts of nutrients, since they lack vitamins, minerals, and fiber. Inflammatory bowel disease is more common in industrialized countries and the authors point out that dietary factors may be related. Similarly, dietary components and foods can have a major impact on gut microbiota.

That said, a recent review published in the journal Nutrients discusses new research on how certain diets, as well as food components and additives, affect the composition of the gut microbiota (Figure 1) (5) (5).

The authors indicate that a food variety is better for gut health and promotes a balanced composition of gut microbiota. On the one hand, a high intake of animal proteins, saturated fats, sugars, and salt could stimulate the growth of pathogenic bacteria to the detriment of beneficial bacteria, which may lead to alterations of the intestinal barrier. On the other hand, the consumption of complex polysaccharides and vegetable protein could be associated with an increase in the amount of beneficial bacteria, stimulating the production of short-chain fatty acids. Additionally, polyphenols, omega-3 fatty acids and micronutrients appear to have the potential to confer health benefits through modulation of the gut microbiota (5).

Therefore, a diet rich in fiber, fruits, vegetables, and greens promotes a healthy composition of the intestinal microbiota and the intestine. The Western dietary pattern, characterized by a high content of ultra-processed foods, may lead to a decrease in beneficial bacteria, which may increase intestinal permeability and inflammation. Experts agree that the Mediterranean dietary pattern remains the solution to optimally modulate the diversity and stability of the microbiota, as well as the regular permeability and activity of the individual’s immune functions.

The Mediterranean diet, centered on fruits, vegetables, olive oil, nuts, legumes, fish, and whole grains, has been linked to a host of health benefits, including alower risk of mortality and the prevention of many diseases, such as cardiovascular disease, diabetes, metabolic syndrome, cognitive impairment, and depression. It is based on the consumption of essential fatty acids, polyphenols, and other antioxidants, a high intake of prebiotic fiber and low glycemic index carbohydrates, and a higher intake of vegetable proteins than animal proteins. This is a dietary pattern that, ultimately, with its benefits modulates a healthy gut microbiota.

Finally, the journal Medicina Clínica recommends the following measures to prevent and combat dysbiosis (2):

• Maintaining a regular oral hygiene to control the microbiota in the mouth
• Maintaining an adequate body mass index (BMI) to prevent metabolic syndrome by losing weight, controlling blood pressure, and exercising regularly
• Avoiding hydrogenated and saturated fats, prioritizing monounsaturated (olive oil) and polyunsaturated omega-3 (rather than omega-6) fatty acids
• Avoiding the indiscriminate and unjustified administration of antibiotics, as well as the ingestion of meat obtained from animals that have been treated with antibiotics or hormones
• Restricting as much as possible cosmetic products or foods containing molecules of dubious efficacy or recognized toxicity (endocrine disruptors)

Finally, the medical and nutritional team here at Neolife analyzes each of the health factors in each individual case, where the role of the microbiota is of special interest due to the latest scientific evidence regarding its impact on disease prevention. Neolife creates a personalized diet, after completing the microbiota analysis, with the goal of modulating and restoring a healthy intestinal microbiota and providing optimal health results. Future advances in the knowledge of the interactions between food compounds and gut bacteria will lead to a better understanding of both positive and negative interactions with dietary habits.

BIBLIOGRAPHY

(1) Gut Microbiota for Health. (2021). “Gut microbiota info”. URL: https://www.gutmicrobiotaforhealth.com/about-gut-microbiota-info/

(2) Chimenos-Küstner, E. et al. (2017). “Disbiosis como factor determinante de enfermedad oral y sistémica: importancia del microbioma” [Dysbiosis as a determining factor of oral and systemic disease: the importance of the microbiome]. Clin. Vol. 149(7): 305-309. URL: https://www.elsevier.es/es-revista-medicina-clinica-2-articulo-disbiosis-como-factor-determinante-enfermedad-S0025775317304414

(3) Icaza-Chávez, M.E. (2013). “Microbiota intestinal en la salud y la enfermedad” [Gut microbiota in health and disease]. Revista de Gastroenterología de México. Vol. 78(4): 240-248. URL: https://www.sciencedirect.com/science/article/pii/S0375090613001468

(4) Narula, N. et al. (2021). “Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study”. BMJ; 374: n1554. URL: https://www.bmj.com/content/374/bmj.n1554

(5) Rinninella, E. et al. (2019). “Food components and dietary habits: keys for a healthy gut microbiota composition”. Nutrients. Vol. 11(10): 2393. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835969/

La entrada Intestinal Diseases and Dysbiosis se publicó primero en Neolife.

Osteoarthritis is better known than arthritis, but this pathology affects at least 300 million people in the world and has a very important impact on quality of life and mortality.

Osteoarthritis is a disease that is still being studied; we may develop it after a trauma or because we have an “inflammatory activation”. The manifestations (areas and degree of involvement) may vary from one individual to another. What is clear is that this disorder affects every element of the joint.

Dr. Celia Gonzalo Gleyzes – Neolife Medical Team

Osteoarthritis (OA) is a serious disease

OA is the most prevalent arthritic problem in the global population over 60 years of age, generally affecting knees, hips, spine, and fingers.

Pain is the first symptom, the one that leads the individual to consult a doctor and the reason, sometimes, for incapacity.

The diagnosis is established by a combination of clinical history, physical examination, and imaging test findings. Blood tests are requested to rule out other diseases.

OA pain is neuropathic and central.

The causes of pain are not completely clear; let us not forget that cartilage is aneural (it lacks nerves), but the bone and synovial membrane can produce stimuli or respond to them, causing painful sensations.

Osteoarthritis is a disease that can limit our daily life (inability to work and even to walk; at this point, I would associate an increase in mortality).

OA, a disease that affects the entire joint

This pathology leads to joint destruction, starting with cartilage degradation. It therefore affects the cartilage, synovial tissue, subchondral bone, tendons, and ligaments. The main players in the onset of the problem are the cartilage, the subchondral bone, and the synovial membrane. These tissues secrete signaling molecules (cytokines) that control the degeneration of the articular cartilage matrix.

The effects of proinflammatory cytokines in OA outweigh the anti-inflammatory effects of other cytokines and growth factors; the joint homeostatic balance is disrupted. This causes the cartilage and bone to degrade, new pathological bone to form, and the osteophytes and the synovial membrane to become inflamed (synovitis).

In some patients, the inflammatory process begins when bits of degraded cartilage come into contact with the synovial tissue. When this tissue becomes inflamed, even more degradative and inflammatory mediators (cytokines, lipid mediators, neuropeptides, and matrix metalloproteinases (MMPs)) are secreted. These mediators cause the chondrocytes (cartilage cells) to produce more MMPs, thereby degrading more cartilage and promoting a vicious inflammatory cycle. Remodeling of the subchondral bone is observed and may even involve the bone marrow. The subchondral bone may also synthesize more inflammatory mediators that contribute to joint degradation.

Synovitis is a potential predictor of structural progression of medial compartment osteoarthritis. The degree of synovitis (in patients without established OA) is sometimes predictive of the patient’s cartilage loss (before it is seen in imaging).

Various origins and presentations of osteoarthritis

Osteoarthritis is a complex pathology whose development may already be preprogrammed by events in early adulthood and adolescence.

There are different phenotypes (expressions of the disease) that can help us to establish a more focused treatment:

• Based on the affected part of the body (hand, knee, hip, spine)
• Based on etiology (origin): obesity/metabolic syndrome, aging, post-trauma, genetics, etc.
• Based on distribution: generalized vs. localized
• Based on the degree of pain
• Initial vs advanced
• Primary vs secondary
• Based on the affected tissues

We will focus our attention on three phenotypes:

• Post-traumatic

The disease is triggered following trauma/damage to any joint tissue (ligaments, synovial tissue, subchondral bone or cartilage). Meniscal fragments or anterior cruciate ligament injuries increase the risk of osteoarthritis, more so if they occur concomitantly.

Innate immunity is particularly important in this process. Joint damage may damage the extracellular matrix, releasing fragments of it that will be recognized by Toll-like receptors. Elevated levels of Toll-like receptors and their ligands are present in cartilage lesions characteristic of osteoarthritis.

• Caused by aging

Inflammation, cellular aging, production of oxygen free radicals lead to increased oxidative stress and chondrocyte aging.

Cellular senescence can be replicative or secretory. There may be chondrocytes with low replication, but with mediator secretion capacity. The problem occurs when they exhibit a senescence-associated secretory phenotype (SASP), i.e. characterized by the secretion of proinflammatory factors.

Oxidative stress contributes to the reduced mitochondrial biogenesis observed in chondrocytes of osteoarthritis patients. A reduction of AMPK (enzyme that detects nutrients and regulates cellular energy metabolism) may also occur, which influences mitochondrial biogenesis and ultimately the repair capacity of chondrocytes.

In an interesting animal model with OA, it was observed that the elimination of senescent (aged) chondrocytes reduced pain and increased the production of new cartilage.

•  Metabolic

The link between obesity and osteoarthritis in weight-bearing joints (knee and hip) has been widely demonstrated. In fact, when patients lose weight, pain and swelling decrease.

The curious thing is that patients with obesity also present a higher incidence of OA of the interphalangeal joints of the hands; this is due to the fact that adipose tissue produces inflammatory mediators, the adipokines. Obesity is also associated with increased intestinal permeability and dysbiosis; metabolites such as lipopolysaccharide (LPS) pass from the gastrointestinal tract into the bloodstream causing low-grade inflammation.

To sum up, metabolic syndrome alters bone remodeling, increases synovial and intra-articular fat inflammation, and increases cartilage catabolism (destruction).

Type 2 diabetes mellitus is also a risk factor for OA (1).

Combating osteoarthritis

After reading these lines, we may deduce that any person could develop this limiting disease that may lead to joint replacement or poly-medication.

It is obvious that slowing down aging, engaging in an adequate and balanced sports activity (avoiding injuries, with supplementation, adapted sports advice, practicing complementary sports), fighting obesity/overweight, controlling cardiovascular risk factors (blood pressure, lipids, and carbohydrate metabolism), treating intestinal dysbiosis (through microbiota studies) are the keys to combating osteoarthritis. One more reason to start taking care of yourself with the help of Neolife.

BIBLIOGRAPHY

(1) Berenbaum F, Walker C. Osteoarthritis and inflammation: a serious disease with overlapping phenotypic patterns. Postgrad Med. 2020 May;132(4):377-384. doi: 10.1080/00325481.2020.1730669. Epub 2020 Feb 26. PMID: 32100608.

(2) Imagen: Robinson, W., Lepus, C.M., Wang, Q., Raghu, H., Mao, R., Lindstrom, T., & Sokolove, J. (2016). Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nature Reviews Rheumatology, 12, 580-592.

La entrada Osteoarthritis: Various Responsible Mechanisms and Patterns se publicó primero en Neolife.

Melatonin is of great importance in COVID-19. In humans, its levels are reduced in DM2, metabolic syndrome, and cardiovascular disease, and its therapeutic value has been demonstrated.

The development of an effective vaccine is crucial to control the disease, especially in the elderly who present impaired immunity. Melatonin has been shown to stimulate the production of interleukin which increases the CD4+ lymphocyte population. Thus, its use in vaccination would enhance immune response, and its duration.

Dr. Alfonso Galán González – Neolife Medical Team

Introduction

In this second part of this series on melatonin and coronavirus, we will discuss the protective effects at the cellular and neuronal level specifically that this molecule has and how it can improve the outcome of vaccination. We’ll also provide some insights into two studies currently underway.

“Mental fog”, a term that describes a state of confusion, forgetfulness, inability to concentrate, fatigue, and low mental energy appears to be a major after effect of COVID-19 disease. In this context, the neuroprotective properties of melatonin deserve some consideration.

Cytoprotective effect

Type 2 diabetes (DM2), metabolic syndrome, and heart disease of ischemic or non-ischemic origin are comorbidities that aggravate COVID-19 disease. The prevalence of metabolic syndrome (a set of cardiovascular risk factors that include a larger waist circumference, high levels of triglycerides, high blood pressure, high glucose, and low HDL cholesterol) worldwide varies from 15 to 30% depending on the region and leads to a 1.5 to 2.5-fold increase in the risk of cardiovascular mortality. According to the CDC (Centers for Disease Control), people with metabolic syndrome are 10 times more likely to die from COVID-19.

And here lies the importance of controlling these diseases during the pandemic.

In humans, melatonin levels are reduced in DM2, metabolic syndrome, and cardiovascular disease, and its therapeutic value has been demonstrated in several studies with doses of 2 to 5 mg daily. In animal models of these diseases, it has demonstrated effectiveness in reducing symptoms. All cells in the body contain melatonin in quantities greater than the circulating melatonin produced in the pineal gland. It is synthesized in the mitochondria, but for unknown reasons this melatonin is not released into the extracellular space. Therefore, to improve intracellular melatonin levels we must use high doses of melatonin, much higher than those used as a chronobiotic agent. Allometric calculations indicate doses in the range of 40 to 100 mg per day for cytoprotective effects.

Neuroprotective effect

Various neurological after effects like anosmia, stroke, paralysis, cranial nerve involvement, encephalopathy, delirium, meningitis, and seizures have been observed in COVID patients. The cause may be the virus itself, thrombotic complications, or an exaggerated cytokine response. Antibodies in cerebrospinal fluid, white matter changes, and psychological and psychiatric consequences are found in these patients.

A study of over 84,000 British patients with varying severities of COVID-19 disease showed in those who were even asymptomatic – regardless of race, age, educational background, income level, or previous illness – a decline of about 10 years on average in global cognitive abilities. The so called “mental fog”, a term that describes this state of confusion, forgetfulness, inability to concentrate, fatigue, and low mental energy appears to be a major after effect of the disease. In this context, the neuroprotective properties of melatonin deserve some consideration.

In the early stages of cognitive decline, patients treated with melatonin show improved performance in several neuropsychological and depression tests, as well as improved sleep quality and ability to stay awake during the day.

The thickness of the lamina cribrosa has been shown to be a marker of neurodegenerative diseases. Another recent study has shown how treatment with doses of melatonin of 0.15 mg/kg in minimal cognitive impairment increases its thickness as well as hippocampal volume, lowering CSF tau levels – a marker of cognitive impairment in cerebrospinal fluid – and improving the results of the Mini-Mental test.

Boosting effect of the vaccine

Initial data from vaccines already in use show some lower protection in older patients. Melatonin may help close that gap.

The existing literature indicates that:

• Melatonin is effective in counteracting the immunosuppression seen in aging, an effect produced by increasing CD4+ T lymphocytes.
• Melatonin is an adjuvant in cancer vaccinations by enhancing the response of CD8+ T lymphocytes (cytotoxic).
• Melatonin enhances the immune response to vaccines by increasing CD4+ T lymphocytes and B cells that produce IgG.

A recent study shows that plasma from convalescent COVID patients has a strong CD4+ response to the Spike protein, which is the target of current vaccines, and that this response was related to IgG and IgA levels.

In some patients, the immune response is not sufficient and cases of reinfection have been documented.

Thus the development of an effective vaccine is crucial to control the disease, especially in the elderly who show lower CD8+ cell counts due to inhibition of IL-2 and IL-2 receptors. Melatonin has been shown to stimulate the production of this Interleukin by increasing CD4+ cells. And so its use in vaccination would enhance the kind of immunity that the vaccine is trying to create by boosting the immune response and its duration over time.

This outline summarizes what we have discussed in these posts on melatonin and COVID.

Now we will present some of the highlights of two studies underway in Spain that seek to study different effects of melatonin in this disease.

Ongoing studies at the HULP (Hospital Universitario La Paz, Madrid) with melatonin in COVID-19

The first one we’ll mention seeks to find out if a low dose of melatonin (2 mg.) may prevent infection in high risk contacts and if patients taking it develop less severe disease. The logic behind this study lies in the observation that children have less severe COVID, and they have very high levels of melatonin. Is this what protects them from severe COVID?

Women, as seen in these graphs, also present a lower mortality rate from COVID-19…and also have higher melatonin levels than men.

The other ongoing study seeks to find out if treatment with very high doses of melatonin in critically ill patients admitted to the ICU improves their prognosis. The available evidence shows that COVID mortality curves are very similar to those of melatonin level decline.

There are data that show that exposure to natural light improves the prognosis of patients with sepsis.

There is also growing evidence that melatonin has a very important effect on sepsis, inflammation, and immunity. Some examples:

These patients will receive intravenous melatonin in doses of 5 mg/kg every 6 hours for 7 days, and we will see if this decreases mortality, length of stay in ICU, need for ventilation, vital organ failure, and thrombotic phenomena.

BIBLIOGRAPHY

(1) Simko, F.; Hrenak, J.; Dominguez-Rodriguez, A.; Reiter, R.J. Melatonin as a putative protection against myocardial injury in COVID-19 infection. Expert Rev. Clin. Pharmacol. 2020, 13, 921–924.

(2) Cardinali, D.P. Melatonin: Clinical perspectives in neurodegeneration. Front. Endocrinol. 2019, 10, 480

(3) Cardinali, D.P.; Vigo, D.E.; Olivar, N.; Vidal, M.F.; Brusco, L.I. Melatonin therapy in patients with Alzheimer’s disease.Antioxidants 2014, 3, 245–277

(4) Cardinali, D.P.; Vigo, D.E.; Olivar, N.; Vidal, M.F.; Furio, A.M.; Brusco, L.I. Therapeutic application of melatonin in mild cognitive impairment. Am. J. Neurodegener. Dis. 2012, 1, 280.

(5) Xu, L.; Yu, H.; Sun, H.; Hu, B.; Geng, Y. Dietary melatonin therapy alleviates the lamina cribrosa damages in patients with mild cognitive impairments: A double-blinded, randomized controlled study. Med. Sci. Monit. 2020, 26, e923232-1.

(6) Cardinali, D.P.; Esquifino, A.I.; Srinivasan, V.; Pandi-Perumal, S.R. Melatonin and the immune system in aging. Neuroimmunomodulation 2008, 15, 272–278.

(7) Moreno, A.C.; Porchia, B.F.; Pagni, R.L.; Souza, P.D.C.; Pegoraro, R.; Rodrigues, K.B.; Barros, T.B.; Aps, L.R.; de Araújo, E.F.; Calich, V.L.; et al. The Combined Use of Melatonin and an Indoleamine 2,3-Dioxygenase-1 Inhibitor Enhances Vaccine-Induced Protective Cellular Immunity to HPV16-Associated Tumors. Front. Immunol. 2018, 9, 1914.

(8) Cardinali DP, Brown GM, Pandi-Perumal SR. Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients?. Diseases. 2020;8(4):44. Published 2020 Nov 26.

La entrada Melatonin in the Time of Pandemic (Part II) se publicó primero en Neolife.

Inflammation is the physiological response of the body to an infection or condition. But chronic inflammatory processes are involved in many health problems.

Chronic systemic inflammation is the leading cause of disability and mortality worldwide. Cancer, diabetes, cardiovascular, autoimmune, and neurodegenerative diseases are all related to inflammation. Experimental research has shown that food components may have adequate anti-inflammatory effects and could reduce the risk of disease.

Alejandro Monzó – Neolife Nutrition Unit

50% of all deaths are attributable to inflammation-related diseases

Inflammation is the immune system’s response to injury or infection. An inflammatory process begins when chemical compounds are released by the damaged tissue, and, in response, white blood cells produce substances that cause cells to divide and grow to rebuild the tissue and help repair the injury (1). Chronic inflammation often begins with a similar cellular response; however, it develops into a persistent state over a much longer period of time.

It may be caused by infections that do not go away, by abnormal immune reactions to tissues or by conditions such as obesity. Over time, oxidative stress resulting from inflammation may cause DNA damage and eventually lead to disease. Therefore, an anti-inflammatory diet consists of eating foods that prevent and reduce inflammation in our body (1,2).

Currently, our diet allows us to incorporate into our body foods with not only nutritional but also protective properties, like phytochemicals, capable of reducing the risk of developing various pathological conditions, including inflammatory-based diseases. Experts at Harvard Medical School point out that inflammation is an important underlying mechanism for the development of chronic diseases, such as type 2 diabetes and heart disease (3).

Among the factors that promote chronic inflammation, the current dietary profile of the general population stands out, characterized by a higher consumption of industrial foods, trans fats, salt, refined cereals, additives, and sugary drinks, together with a high consumption of alcohol and low consumption of fruits, vegetables and foods rich in dietary fiber (4,5). Decreasing the consumption of these pro-inflammatory foods and increasing the consumption of healthy, anti-inflammatory foods like fruits, and vegetables, especially leafy greens, may be effective in reducing these chronic diseases and associated mortality (4,5). This healthy diet should be accompanied by additional measures, such as avoiding smoking, alcohol, and chronic stress, combating overweight, and doing regular physical activity and exercise (2).

One of the long-term harmful elements of chronic inflammation is an acceleration of the oxidation processes of our cellular structures, which, in practice, is equivalent to accelerating their aging. The Spanish Society of Endocrinology and Nutrition (SEEN) points out the importance of respecting the nocturnal fasting period within the wake-sleep cycle to prevent oxidation (6). Within the normal biological cycle, the human being alternates between periods in which food is ingested and processed with periods of fasting in which metabolic pathways change and balance. If we’re always ingesting food, at night or throughout the day nonstop, the mechanisms of hormonal regulation of the metabolism are profoundly altered, since processing food means setting in motion the necessary oxidative processes. Therefore, the presence of antioxidant substances in certain foods can be a good defense strategy from a nutritional point of view.

Food thus becomes a factor in the modulation of the inflammatory response. Phytochemicals present in food, in their original form or when metabolized, can form active metabolites and behave as intracellular messengers activating or inhibiting the expression of genes involved in inflammatory processes. Therefore, one of the diets that has this characteristic is the Mediterranean diet, rich in fruits, vegetables, legumes, whole grains, fish, nuts and healthy oils, which promotes the reduction of cardiovascular events, cancer, and chronic diseases (3,4,7).

An anti-inflammatory diet offers benefits to all age groups of the population, regardless of their health or physiological condition (8). It requires eating more fresh, seasonal foods and avoiding processed foods. The goal is to eat foods rich in vitamins, minerals, antioxidants, fiber and healthy fatty acids, especially omega-3, such as those presented below (3,5,7):

• Green leafy vegetables: spinach, kale, Swiss chard
• Cruciferous vegetables: broccoli, cabbage, cauliflower, Brussels sprouts
• Tomato
• Fruits: citrus fruits, red fruits, orange, apple, pomegranate, strawberries, grapes
• Beverages: tea and coffee
• Nuts and seeds: walnuts and almonds
• Oily fish: salmon, tuna, sardines, mackerel
• Legumes
• Olive oil
• Dark chocolate
• Spices and plants: turmeric, ginger, cinnamon

In particular, fruits and vegetables like blueberries, apples, and leafy greens have natural antioxidants and polyphenols, protective compounds with great benefits. Studies have also associated nuts in particular with reduced markers of inflammation and a lower risk of cardiovascular disease and diabetes. Coffee and tea contain polyphenols and other anti-inflammatory compounds, which may also protect against inflammation (3).

Processed meats (hamburgers, sausages, cold cuts), potatoes and other fried foods, refined carbohydrates from pastries and cakes, sugary drinks, margarines and unhealthy and poor quality oils have been shown to be pro-inflammatory foods, whose consumption we should avoid and reduce due to their increased risk of chronic diseases such as cancer, especially colorectal cancer (4,5). Moreover, choosing less aggressive forms of cooking better preserves thermolabile elements (some vitamins and minerals) and generates fewer oxidative processes in the food, reducing the inflammatory load (6). Likewise, a study published in the Journal of Internal Medicine reported a link between following a diet with high anti-inflammatory potential and a longer life span and lower death rate from cardiovascular disease and cancer, with smokers particularly benefiting from the diet (5).

Therefore, current scientific evidence shows that eating a variety of nutritious foods can help reduce inflammation in the body. Our diet can help prevent and keep chronic inflammation under control, and especially a healthy eating pattern provides nutrients that support a healthy immune system. More studies are needed to draw conclusions about how these foods affect inflammation, and we still don’t know how much and how often “anti-inflammatory” foods should be consumed. For all these reasons, the Academy of Nutrition and Dietetics shows us dietary approaches that may help reduce inflammation (9):

1. Increase the intake of vegetables and fruits, making sure they are at least half of what we eat, with great variety and color.
2. Prioritize the consumption of quality proteins. Choose legumes, vegetable protein, lean cuts of meat, oily fish, and low-fat dairy products.
3. Choose healthy fats, like extra virgin olive oil, nuts, avocado, canola oil, foods rich in omega 3, and seeds.
4. Choose whole grains and legumes. This way, more dietary fiber is included in the diet, like brown rice, quinoa, millet…
5. Experiment with fresh herbs and spices, adding flavor to dishes and recipes.
6. Always take into account other lifestyle factors: getting enough sleep (both quality and duration of sleep have a direct impact on inflammation), staying active (30 to 60 minutes of moderate-intensity physical activity per day most days of the week has anti-inflammatory effects), and maintaining a healthy body weight (excess body fat may contribute to increased inflammation).

Finally, Neolife’s medical and nutrition team studies and analyzes the longitudinal monitoring of our patients analytical biomarkers on a regular basis, where inflammation is a key health metric. There is strong scientific evidence that suggests that eating and lifestyle habits play a part in our health and disease prevention. Changing our dietary pattern towards a healthier, more balanced and varied one, rich in antioxidants and phytochemicals, and displacing the consumption of unhealthy foods, may reduce the inflammatory load. It is in our hands to take the step towards adopting a healthy lifestyle, the key component to the success of our integral health program.

BIBLIOGRAPHY

(1) (2015). “Chronic inflammation”. National Cancer Institute. URL: https://www.cancer.gov/about-cancer/causes-prevention/risk/chronic-inflammation

(2) Zhu, F., Du, B. & Xu, B. (2018). “Anti-inflammatory effects of phytochemicals from fruits, vegetables and food legumes: A review”. Critical Reviews in Food Science and Nutrition. Vol. 58(8): 1260-1270. URL: https://pubmed.ncbi.nlm.nih.gov/28605204/

(3) Harvard Medical School. (2020). “Foods that fight inflammation”. Harvard Health Publishing. URL: https://www.health.harvard.edu/staying-healthy/foods-that-fight-inflammation

(4) De Luis Román, D.A. Bellido Guerrero, D. García Luna, P.P. Olivera Fuster, G. (2017). “Dietoterapia, nutrición clínica y metabolismo” [Diet therapy, clinical nutrition and metabolism]. Third Edition. Sociedad Española de Endocrinología y Nutrición. Grupo Aula Médica, S.L. Madrid, Spain.

(5) Parra-Soto, S. et al. (2020). “An anti-inflammatory diet is associated with lower mortality risk from all causes”. Letter to the editor. Rev Med Chile. Vol. 148: 1860-1867. URL: https://scielo.conicyt.cl/scielo.php?pid=S0034-98872020001201863&script=sci_arttext

(6) Botella, F. Dieta Antiinflamatoria [Anti-inflammatory Diet]. SEEN. URL: https://www.seen.es/ModulGEX/workspace/publico/modulos/web/docs/apartados/2268/050421_125415_2682718942.pdf

(7) Caballero-Gutiérrez, L. & Gonzáles, G. (2016). “Alimentos con efecto anti-inflamatorio” [Foods with anti-inflammatory effect]. Acta Médica Peruana. Vol. 33(1): 50-64. URL: https://www.scielo.org.pe/pdf/amp/v33n1/a09v33n1.pdf

(8) Barry Sears PhD. (2015). “Anti-inflammatory diets”. Journal of the American College of Nutrition. Vol. 34(1): 14-21. URL: https://pubmed.ncbi.nlm.nih.gov/26400429/

(9) Eat Right. (2019). “Can diet help with inflammation?”. Academy of Nutrition and Dietetics. URL: https://www.eatright.org/health/wellness/preventing-illness/can-diet-help-with-inflammation

La entrada The Effects of an Anti-inflammatory Diet se publicó primero en Neolife.

Cellular senescence is one of the 9 ‘‘Hallmarlks of Aging”. Some, but not all, senescent cells may acquire what we call a senescence-associated secretory phenotype (SASP).

Cellular senescence is related in one way or another to most diseases and syndromes associated with aging. We have the possibility of acting on it by influencing the aging process, the onset of diseases, and syndromes associated with age.

Dr. Alfonso Galán González – Neolife Medical Team

Introduction

Senescent cells are cells that do not die, but stop replicating, become “immortal” by resisting apoptosis (programmed cell death), and are often still very active. Hence the nickname “zombie cells”.

In this blog post, we’ll take an in depth look into one of those 9 “Hallmarks of aging”, determinants of aging, or molecular mechanisms of aging so often discussed in these texts: cellular senescence.

Why talk about cellular senescence?

• Cellular senescence is related in one way or another to the remaining 8 mechanisms.
• It is behind most diseases and syndromes associated with aging.
• We have the possibility of acting on it by influencing the aging process, the onset of diseases, and syndromes associated with age.

I believe that this more than justifies the relevance of this article and others to come, which will go into the strategies we have to combat it.

Aging

Aging is associated with the risk of developing multiple chronic diseases, geriatric syndromes, worsening physical resilience, and mortality. These risks increase exponentially in the last quarter of our lives.

Among the diseases for which age is a major risk factor we find:

Heart failure, myocardial infarction, dementia, stroke, cancer, diabetes and metabolic diseases, kidney dysfunction, chronic pulmonary disease, osteoporosis, arthritis, blindness, etc….

Geriatric syndromes include frailty, muscle loss, falls, incontinence, and moderate cognitive impairment, among others.

A worsened resilience manifests itself as slower recovery after heart attacks, strokes, injuries, surgeries, greater severity of infections like the flu or coronavirus, and a lower generation of antibodies after vaccination. The cause of all these pathologies and processes that limit human life and capabilities lies in these aging markers.

We know that cellular senescence contributes to the development of inflammation, fibrosis, DNA damage, development of protein aggregates, autophagy failure, lipotoxicity, mitochondrial dysfunction, NAD+ depletion, reactive oxygen species (ROS), and stem, progenitor, and immune cell dysfunction.

Cellular Senescence

Cellular senescence was first described in 1961 by Hayflick and Moorehead as a cellular fate of irreversible cessation of replication, maintained viability with resistance to apoptosis and, most often, an increase in metabolic activity. In other words, these are cells that do not die, but stop replicating, become “immortal” by resisting apoptosis (programmed cell death), and are often still very active.

These characteristics are what have led them to be colloquially called “zombie cells”. The causes that lead a cell to take this path are varied and include signals associated with tissue or cell damage and cancer development. These include:

• DNA damage
• Telomere shortening
• Exposure to extracellular DNA
• Activation of oncogenes
• Replication stress or proliferation inducers
• Protein aggregates and unstructured proteins
• Failure of protein recycling due to decreased autophagy
• Presence of AGEs (advanced glycation end products like hemoglobin)
• Saturated lipids or bioactive lipids like bradykinin or prostaglandins
• Reactive metabolites like ROS
• Mechanical stress like the one associated with the lack of cartilage in osteoarthritis or the one produced in atheroma plaques
• Inflammatory cytokines like TNF⍺
• DAMPS and PAMPS (damage associated molecular patterns and pathogen associated molecular patterns), i.e., intracellular contents released into the environment when bacterial cells or endotoxins are destroyed

Well, whatever the stimulus may be, one or more of the transcription factor cascades that promote this state of senescence (p16 INK4a, p53, p21, Rb, etc.) are activated.

From our cell culture data, it takes 10 days to 6 weeks for the cells to reach a complete state of senescence. This has important implications for treatment, as we will see when we discuss senolytics.

What makes the accumulation of senescent cells so bad, and why do we want to eliminate them? Some, but not all, senescent cells may acquire what we call a senescence-associated secretory phenotype (SASP). This means that these cells are going to secrete:

• Proinflammatory, proapoptotic, and insulin resistance-inducing cytokines like TNF⍺, IL6, IL8, and others
• Chemokines that attract, activate, and anchor immune cells
• Metalloproteases that cause tissue destruction
• Members of the TGFß family that lead to fibrosis and stem and progenitor cell dysfunction
• Activins and inhibins that also affect stem and progenitor cells
• Other factors like serpins that lead to thrombosis and fibrosis
• Growth factors that may lead to tumor dissemination
• Bioactive lipids like prostaglandins, bradykinin, and ceramides that lead to inflammation and tissue dysfunction
• MicroRNAs that also lead to stem and progenitor cell dysfunction, inflammation, and insulin resistance
• Exosomes that carry these cytotoxic and senescence-inducing signals to neighboring or distant sites

The senescent cells that acquire this secretory phenotype are 30 to 70% of those present, and the mediators they produce depend on the type of senescent cell and the cause that originated their conversion.

Cells that do not acquire this secretory phenotype are called “helper” cells that do not seem to release proinflammatory or proapoptotic factors, but the true utility of these cells and their interrelationship with the secretory ones has not yet been elucidated.

This secretory phenotype may be modulated by many factors such as hormonal environment, drugs, or pathogens.

Like everything in our bodies, it seems that the presence of senescent cells has some beneficial function; in fact, they have been associated with tissue remodeling during development and healing and even defense against cancer. Some research suggests that if we interfere with these senescence cascades, we may promote the development of cancer. However, getting rid of already formed senescent cells, many of which carry oncogenic mutations or lead to cancer formation because of their secretory phenotype, prevents or delays cancer development. Many studies using senolytic agents confirm this last point.

Although senescent cells may appear in human and other vertebrate tissues at any point in their lives, they accumulate in the later part of their lives. For example, cutaneous senescent cells increase dramatically from age 60 to 80 in otherwise healthy humans.

Senescent cells accumulate at the sites where many diseases originate throughout life. For example, in adipose tissue in diabetes and obesity, in the hippocampus and frontal cortex in Alzheimer’s, in the substantia nigra in Parkinson’s, in bones and bone marrow in osteoporosis, in lungs in pulmonary fibrosis, in the liver in cirrhosis, in the retina in AMD (age-related macular degeneration), in plaques in psoriasis, in kidneys in kidney disease, in the endothelium in preeclampsia, in the heart and arteries in cardiovascular diseases…. Interesting, isn’t it? This is certainly not a chance occurrence.

Precisely to demonstrate that this is not a coincidence, there are experiments in which senescent cells are injected to determine causality, i.e., to cause disease by introducing senescent cells into a tissue.

After introducing senescent cells into the knees of young mice, they caused a state of osteoarthritis with radiological and clinical findings similar to those of “natural” osteoarthritis. After injecting them with non-senescent cells, this did not happen. Other studies of the same type have caused frailty, a higher mortality, and kidney failure in healthy mice.

In our next article, we will discuss the drugs and supplements that are being investigated to selectively kill these senescent cells, which are called senolytics, and the fascinating results we have obtained so far.

BIBLIOGRAPHY

(1) Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020;288(5):518-536. doi:10.1111/joim.13141

(2) Robbins PD, Jurk D, Khosla S, et al. Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span. Annu Rev Pharmacol Toxicol. 2021;61:779-803. doi:10.1146/annurev-pharmtox-050120-105018

(3) Demaria M, Ohtani N, Youssef SA et al An essential role for senescent cells in optimal wound healing through secretion of PDGF‐AA. Dev Cell 2014; 31: 722–33

(4) Campisi J. Aging, cellular senescence, and cancer. Ann Rev Physiol 2013; 75: 685–705

(5) Xu M, Pirtskhalava T, Farr JN et al Senolytics improve physical function and increase lifespan in old age. Nat Med 2018; 24: 1246–56.10.1038/s41591-018-0092-9

(6) Chinta SJ, Woods G, Demaria M et al Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to parkinson’s disease. Cell Rep 2018; 22: 930–40.

(7) Sun S, Cai B, Li Y et al HMGB1 and Caveolin‐1 related to RPE cell senescence in age‐related macular degeneration. Aging 2019; 11: 4323–37.

(8) Xu M, Bradley EW, Weivoda MM et al Transplanted senescent cells induce an osteoarthritis‐like condition in mice. J Gerontol A Biol Sci Med Sci 2017; 72: 780–5.

(9) Kim SR, Jiang K, Ferguson CM et al Transplanted senescent renal scattered tubular‐like cells induce injury in the mouse kidney. Am J Physiol Renal Physiol 2020; 318: F1167–F76.

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