Tryptophan – Niacin – NAD = Anti-aging

tryp foodtryptryptophan and niacin

Chocolate, oats, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas, almonds, sunflower seeds, pumpkin seeds, buckwheat, spirulina, bananas, and peanuts.

Tryptophan

For many organisms (including humans), tryptophan is needed to prevent illness or death, but cannot be synthesized by the organism and must be ingested; in short, it is an essential amino acid. Amino acids, including tryptophan, act as building blocks in protein biosynthesis, and proteins are required to sustain life. In addition, tryptophan functions as a biochemical precursor for the following compounds (see also figure to the right):

  • Serotonin (a neurotransmitter), synthesized via tryptophan hydroxylase.[9][10] Serotonin, in turn, can be converted to melatonin (a neurohormone), via N-acetyltransferase and 5-hydroxyindole-O-methyltransferase activities.[11]
  • Niacin, also known as vitamin B3, is synthesized from tryptophan via kynurenine and quinolinic acids as key biosynthetic intermediates.[12]
  • Auxins (a class of phytohormones) are synthesized from tryptophan.[13]
  • The disorder fructose malabsorption causes improper absorption of tryptophan in the intestine, reduced levels of tryptophan in the blood,[14] and depression.[15] Some studies did not find reduced tryptophan in cases of lactose maldigestion.[14]
  • Niacin and its derivative nicotinamide are dietary precursors of nicotinamide adenine dinucleotide (NAD), which can be phosphorylated (NADP) and reduced (NADH and NADPH). NAD functions in oxidation-reduction (redox) reactions and non-redox reactions. (More information)
  • Pellagra is the disease of severe niacin deficiency. It is characterized by symptoms affecting the skin, the digestive system, and the nervous system and can lead to death if left untreated. (More information)
  • Dietary tryptophan can be converted to niacin, although the efficiency of conversion is low in humans and affected by deficiencies in other nutrients. (More information)
  • Causes of niacin deficiency include inadequate oral intake, poor bioavailability from unlimed grains, defective tryptophan absorption, metabolic disorders, and the long-term use of chemotherapeutic treatments. (More information)
  • The requirements for niacin are based on the urinary excretion of niacin metabolites. (More information)
  • NAD is the sole substrate for PARP enzymes involved in DNA repair activity in response to DNA strand breaks; thus, NAD is critical for genome stability. Several studies, mostly using in vitro and animal models, suggest a possible role for niacin in cancer prevention. Nevertheless, large studies are needed to investigate the association between niacin deficiency and cancer risk in human populations. (More information)
  • Despite promising initial results, nicotinamide administration has failed to prevent or delay the onset of type 1 diabetes in high-risk relatives of type 1 diabetics. Future research might explore the use of nicotinamide in combined therapy and evaluate activators of NAD-dependent enzymes. (More information)
  • At pharmacologic doses, niacin, but not nicotinamide, improves the lipid profile and reduces coronary events and total mortality in patients at high risk for coronary heart disease. Several clinical trials have explored the cardiovascular benefit of niacin in combination with other lipid-lowering medications. (More information)
  • Elevated tryptophan breakdown and niacin deficiency have been reported in HIV-positive people. This population is also at high risk for cardiovascular disease, and current data show that they could benefit from niacin supplementation. (More information)
  • The tolerable upper intake level (UL) for niacin is based on skin flushing, niacin’s most prominent side effect. A new drug, laropiprant, has been developed to reduce skin flushing. Adverse effects have also been reported with pharmacologic doses of niacin administrated alone or in combination with other lipid-lowering medications. (More information)
  • Niacin is a water-soluble vitamin, which is also known as nicotinic acid or vitamin B3. Nicotinamide is the derivative of niacin and used by the body to form the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The chemical structures of the various forms of niacin are shown (Figure 1). None of the forms are related to the nicotine found in tobacco, although their names are similar (1).

Function

  • Oxidation-reduction (redox) reactions
  • Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes involving the transfer of electrons. Over 400 enzymes require the niacin coenzymes, NAD and NADP, mainly to accept or donate electrons for redox reactions (2). NAD functions most often in energy-producing reactions involving the degradation (catabolism) of carbohydrates, fats, proteins, and alcohol. NADP functions more often in biosynthetic (anabolic) reactions, such as in the synthesis of all macromolecules, including fatty acids and cholesterol (1, 3).

Non-redox reactions

  • The niacin coenzyme, NAD, is the substrate (reactant) for at least four classes of enzymes that separate the nicotinamide moiety from NAD and transfer ADP-ribose to acceptors.
  • Mono-ADP-ribosyltransferase enzymes were first discovered in certain bacteria, where they mediate the action of toxins, such as cholera and diptheria. In mammalian cells, these enzymes transfer an ADP-ribose residue from NAD to a specific amino acid of a target protein, with the creation of an ADP-ribosylated protein and the release of nicotinamide. Mono ADP-ribosylation reactions reversibly modify the activity of acceptor proteins, such as G-proteins that bind guanosine-5′-triphosphate (GTP) and act as intermediaries in a number of cell-signaling pathways (4).
  • Poly-ADP-ribose polymerases (PARPs) are enzymes that catalyze the transfer of polymers of ADP-ribose from NAD to acceptor proteins. PARPs appear to function in DNA repair and stress responses, cell signaling, transcription, regulation, apoptosis, chromatin structure, and cell differentiation, suggesting a role for NAD in cancer prevention (3). At least six different PARPs have been identified, and although their functions are not yet fully understood, their existence indicates a potential for considerable consumption of NAD (5, 6).
  • A new nomenclature has been proposed for enzymes catalyzing ADP-ribosylation: The PARP family was renamed ARTD, while ARTC designates the mono ADP-ribosyltransferase family (6).
  • ADP-ribosylcyclases catalyze the formation of cyclic ADP-ribose from ADP-ribose. Cyclic ADP-ribose works within cells to provoke the release of calcium ions from internal storage sites and probably also plays a role in cell signaling (1).
  • Sirtuins are a class of NAD-dependent deacetylase enzymes that remove acetyl groups from the acetylated lysine residues of target proteins. During the deacetylation process, an ADP-ribose is added to the acetyl group to produce O-acetyl-ADP-ribose. Both acetylation and ADP-ribosylation are known post-translational modifications that affect protein activities. The initial interest in sirtuins followed the discovery that their activation could mimic calorie restriction, which has been shown to increase lifespan in lower organisms. Such a role in mammals is controversial, although sirtuins are energy-sensing regulators involved in signaling pathways that could play important roles in delaying the onset of age-related diseases (e.g., cardiovascular disease, cancer, dementia, arthritis). To date, the spectrum of their biological functions include gene silencing, DNA damage repair, cell cycle regulation, and cell differentiation (7).

Summary

  • Niacin and its derivative nicotinamide are dietary precursors of nicotinamide adenine dinucleotide (NAD), which can be phosphorylated (NADP) and reduced (NADH and NADPH). NAD functions in oxidation-reduction (redox) reactions and non-redox reactions. (More information)
  • Pellagra is the disease of severe niacin deficiency. It is characterized by symptoms affecting the skin, the digestive system, and the nervous system and can lead to death if left untreated. (More information)
  • Dietary tryptophan can be converted to niacin, although the efficiency of conversion is low in humans and affected by deficiencies in other nutrients. (More information)
  • Causes of niacin deficiency include inadequate oral intake, poor bioavailability from unlimed grains, defective tryptophan absorption, metabolic disorders, and the long-term use of chemotherapeutic treatments. (More information)
  • The requirements for niacin are based on the urinary excretion of niacin metabolites. (More information)
  • NAD is the sole substrate for PARP enzymes involved in DNA repair activity in response to DNA strand breaks; thus, NAD is critical for genome stability. Several studies, mostly using in vitro and animal models, suggest a possible role for niacin in cancer prevention. Nevertheless, large studies are needed to investigate the association between niacin deficiency and cancer risk in human populations. (More information)
  • Despite promising initial results, nicotinamide administration has failed to prevent or delay the onset of type 1 diabetes in high-risk relatives of type 1 diabetics. Future research might explore the use of nicotinamide in combined therapy and evaluate activators of NAD-dependent enzymes. (More information)
  • At pharmacologic doses, niacin, but not nicotinamide, improves the lipid profile and reduces coronary events and total mortality in patients at high risk for coronary heart disease. Several clinical trials have explored the cardiovascular benefit of niacin in combination with other lipid-lowering medications. (More information)
  • Elevated tryptophan breakdown and niacin deficiency have been reported in HIV-positive people. This population is also at high risk for cardiovascular disease, and current data show that they could benefit from niacin supplementation. (More information)
  • The tolerable upper intake level (UL) for niacin is based on skin flushing, niacin’s most prominent side effect. A new drug, laropiprant, has been developed to reduce skin flushing. Adverse effects have also been reported with pharmacologic doses of niacin administrated alone or in combination with other lipid-lowering medications. (More information)
  • Niacin is a water-soluble vitamin, which is also known as nicotinic acid or vitamin B3. Nicotinamide is the derivative of niacin and used by the body to form the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The chemical structures of the various forms of niacin are shown (Figure 1). None of the forms are related to the nicotine found in tobacco, although their names are similar (1).
  • Figure 1. Chemical Structures of Niacin and Related Compounds. Niacin is also known as nicotinic acid or vitamin B3. nicotinamide is the derivative of niacin that is used to form the coenzymes NAD and NADP.

Function

  • Oxidation-reduction (redox) reactions
  • Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes involving the transfer of electrons. Over 400 enzymes require the niacin coenzymes, NAD and NADP, mainly to accept or donate electrons for redox reactions (2). NAD functions most often in energy-producing reactions involving the degradation (catabolism) of carbohydrates, fats, proteins, and alcohol. NADP functions more often in biosynthetic (anabolic) reactions, such as in the synthesis of all macromolecules, including fatty acids and cholesterol (1, 3).

Non-redox reactions

  • The niacin coenzyme, NAD, is the substrate (reactant) for at least four classes of enzymes that separate the nicotinamide moiety from NAD and transfer ADP-ribose to acceptors.
  • Mono-ADP-ribosyltransferase enzymes were first discovered in certain bacteria, where they mediate the action of toxins, such as cholera and diptheria. In mammalian cells, these enzymes transfer an ADP-ribose residue from NAD to a specific amino acid of a target protein, with the creation of an ADP-ribosylated protein and the release of nicotinamide. Mono ADP-ribosylation reactions reversibly modify the activity of acceptor proteins, such as G-proteins that bind guanosine-5′-triphosphate (GTP) and act as intermediaries in a number of cell-signaling pathways (4).
  • Poly-ADP-ribose polymerases (PARPs) are enzymes that catalyze the transfer of polymers of ADP-ribose from NAD to acceptor proteins. PARPs appear to function in DNA repair and stress responses, cell signaling, transcription, regulation, apoptosis, chromatin structure, and cell differentiation, suggesting a role for NAD in cancer prevention (3). At least six different PARPs have been identified, and although their functions are not yet fully understood, their existence indicates a potential for considerable consumption of NAD (5, 6).
  • A new nomenclature has been proposed for enzymes catalyzing ADP-ribosylation: The PARP family was renamed ARTD, while ARTC designates the mono ADP-ribosyltransferase family (6).
  • ADP-ribosylcyclases catalyze the formation of cyclic ADP-ribose from ADP-ribose. Cyclic ADP-ribose works within cells to provoke the release of calcium ions from internal storage sites and probably also plays a role in cell signaling (1).
  • Sirtuins are a class of NAD-dependent deacetylase enzymes that remove acetyl groups from the acetylated lysine residues of target proteins. During the deacetylation process, an ADP-ribose is added to the acetyl group to produce O-acetyl-ADP-ribose. Both acetylation and ADP-ribosylation are known post-translational modifications that affect protein activities. The initial interest in sirtuins followed the discovery that their activation could mimic calorie restriction, which has been shown to increase lifespan in lower organisms. Such a role in mammals is controversial, although sirtuins are energy-sensing regulators involved in signaling pathways that could play important roles in delaying the onset of age-related diseases (e.g., cardiovascular disease, cancer, dementia, arthritis). To date, the spectrum of their biological functions include gene silencing, DNA damage repair, cell cycle regulation, and cell differentiation (7).

Deficiency: Pellagra

  • The late stage of severe niacin deficiency is known as pellagra. Early records of pellagra followed the widespread cultivation of corn in Europe in the 1700s (1). The disease is generally associated with poorer social classes whose chief dietary staple consisted of cereals like corn or sorghum. Pellagra was also common in the southern United States during the early 1900s where income was low and corn products were a major dietary staple (8).
  • Interestingly, pellagra was not known in Mexico, where corn was also an important dietary staple and much of the population was also poor. In fact, corn contains appreciable amounts of niacin, but it is present in a bound form that is not nutritionally available to humans. The traditional preparation of corn tortillas in Mexico involves soaking the corn in a lime (calcium oxide) solution, prior to cooking. Heating the corn in an alkaline solution results in the release of bound niacin, increasing its bioavailability (9).
  • The most common symptoms of niacin deficiency involve the skin, the digestive system, and the nervous system (3). The symptoms of pellagra are commonly referred to as the three D’s: dermatitis, diarrhea, and dementia. A fourth D, death, occurs if pellagra is left untreated (10). In the skin, a thick, scaly, darkly pigmented rash develops symmetrically in areas exposed to sunlight. In fact, the word “pellagra” comes from “pelle agra,” the Italian phrase for rough or raw skin. Symptoms related to the digestive system include inflammation of the mouth and tongue (“bright red tongue”), vomiting, constipation, abdominal pain, and ultimately, diarrhea.
  • Gastrointestinal disorders and diarrhea contribute to the ongoing malnourishment of the subjects. Neurologic symptoms include headache, apathy, fatigue, depression, disorientation, and memory loss and are more consistent with delirium than with the historically described dementia (11). Disease presentations vary in appearance since the classic triad rarely presents in its entirety. The absence of dermatitis, for example, is known as pellagra sine pellagra.

Treatment of pellagra

  • To treat pellagra, the World Health Organization (WHO) recommends administering nicotinamide to avoid the flushing commonly caused by niacin (see Safety). Treatment guidelines suggest using 300 mg nicotinamide per day orally in divided doses, or 100 mg per day parenterally in divided doses, for three to four weeks (12, 13). Because patients with pellagra often display additional vitamin deficiencies, administration of a vitamin B-complex preparation is advised.

Tryptophan metabolism

  • In addition to its synthesis from dietary niacin, NAD can be synthesized from the dietary amino acid tryptophan via the kynurenine pathway (see Figure 2 below). The relative ability to make this conversion varies greatly from mice to humans. The first step is catalyzed by the extrahepatic enzyme indoleamine 2,3-dioxygenase (IDO), which is responsible for the oxidative cleavage of tryptophan. The chronic stimulation of tryptophan oxidation, mediated by an increased activity of IDO and/or inadequate niacin levels, is observed in a number of diseases, including human immunodeficiency virus (HIV) infection (see HIV/AIDS). In healthy individuals, less than 2% of dietary tryptophan is converted to NAD by this tryptophan oxidation pathway (14).
  • Tryptophan metabolism plays an essential regulatory role by mediating immunological tolerance of the fetus during pregnancy (15). It is now understood that tryptophan oxidation in the placenta drives a physiologic tryptophan depletion that impairs the function of nearby maternal T-lymphocytes and prevents the rejection of the fetus. However, the synthesis of niacin from tryptophan is a fairly inefficient pathway that depends on enzymes requiring vitamin B6 and riboflavin, as well as an enzyme containing heme (iron). On average, 1 milligram (mg) of niacin can be synthesized from the ingestion of 60 mg of tryptophan. The term “niacin equivalent” (NE) is used to describe the contribution to dietary intake of all the forms of niacin that are available to the body.
  • Thus, 60 mg of tryptophan are considered to be 1 mg NE. However, studies of pellagra in the southern US during the early twentieth century indicated that the diets of many individuals who suffered from pellagra contained enough NE to prevent pellagra (10), challenging the idea that 60 mg of dietary tryptophan are equivalent to 1 mg of niacin. In particular, one study in young men found that the tryptophan content of the diet had no effect on the decrease in red blood cell niacin content that resulted from low dietary niacin (16).

Causes of niacin deficiency

  • Niacin deficiency or pellagra may result from inadequate dietary intake of niacin and/or tryptophan. As mentioned above, other nutrient deficiencies may also contribute to the development of niacin deficiency. Niacin deficiency, often associated with malnutrition, is observed in the homeless population, in individuals suffering from anorexia nervosa or obesity, and in consumers of diets high in maize and poor in animal proteins (17-20).
  • Patients with Hartnup’s disease, a hereditary disorder resulting in defective tryptophan absorption, have developed pellagra (3). Other malabsorptive states that can lead to pellagra include Crohn’s disease and megaduodenum (21, 22). Carcinoid syndrome, a condition of increased secretion of serotonin and other catecholamines by carcinoid tumors, may also result in pellagra due to increased utilization of dietary tryptophan for serotonin rather than niacin synthesis. Further, prolonged treatment with the anti-tuberculosis drug Isoniazid has resulted in niacin deficiency (23).
  • Other pharmaceutical agents, including the immunosuppressive drugs Azathioprine and 6-Mercaptopurine, the anti-cancer drug 5-Fluorouracil, and Carbidopa, a drug given to people with Parkinson’s disease, are known to increase the reliance on dietary niacin by interfering with the tryptophan-kinurenine-niacin pathway. Finally, other populations at risk for niacin deficiency include dialysis patients, cancer patients (13, 24), individuals suffering from chronic alcoholism (11), and people with HIV (see HIV/AIDS).

Disease Prevention: Cancer

  • Studies of cultured cells (in vitro) provide evidence that NAD content influences mechanisms that maintain genomic stability. Loss of genomic stability, characterized by a high rate of damage to DNA and chromosomes, is a hallmark of cancer (28). The current understanding is that the pool of NAD is decreased during niacin deficiency and that it affects the activity of NAD-consuming enzymes rather than redox and metabolic functions (29). Among NAD-dependent reactions, poly ADP-ribosylations catalyzed by PARP enzymes are critical for the cellular response to DNA injury. After DNA damage, PARPs are activated.
  • The subsequent poly ADP-ribosylations of a number of signaling and structural molecules by PARPs were shown to facilitate DNA repair at DNA strand breaks. Cellular depletion of NAD has been found to decrease levels of the tumor suppressor protein p53, a target for poly ADP-ribosylation, in human breast, skin, and lung cells (27). The expression of p53 was also altered by niacin deficiency in rat bone marrow cells (30). Impairment of DNA repair caused by niacin deficiency could lead to genomic instability and drive tumor development in rat models (31, 32).
  • Both PARPs and sirtuins have been recently involved in the maintenance of heterochromatin, a chromosomal domain associated with genome stability, as well as in transcriptional gene silencing, telomere integrity, and chromosome segregation during cell division (33, 34). Neither the cellular NAD content nor the dietary intake of NAD precursors (niacin and tryptophan) necessary for optimizing protective responses following DNA damage has been determined, but both are likely to be higher than that required for the prevention of pellagra.

Bone marrow

  • Cancer patients often suffer from bone marrow suppression following chemotherapy, given that bone marrow is one of the most proliferative tissues in the body and thus a primary target for chemotherapeutic agents. Niacin deficiency was found to decrease bone marrow NAD and poly-ADP-ribose levels and increase the risk of chemically induced leukemia in rats (35). Conversely, a pharmacologic dose of niacin was able to increase NAD and poly ADP-ribose in bone marrow and decrease the development of leukemia in rats (36).
  • It has been suggested that niacin deficiency often observed in cancer patients could sensitize bone marrow tissue to the suppressive effect of chemotherapy. However, little is known regarding cellular NAD levels and the prevention of DNA damage or cancer in humans. One study in two healthy individuals involved elevating NAD levels in blood lymphocytes by supplementation with 100 mg/day niacin for eight weeks.
  • Compared to non-supplemented individuals, the supplemented individuals had reduced DNA strand breaks in lymphocytes exposed to free radicals in a test tube assay (37). However, niacin supplementation of up to 100 mg/day in 21 healthy smokers failed to provide any evidence of a decrease in cigarette smoke-induced genetic damage in blood lymphocytes compared to placebo (38).
  • More recently, the frequency of chromosome translocation was used to evaluate DNA damage in peripheral blood lymphocytes of 82 pilots chronically exposed to ionizing radiation, a known human carcinogen. In this observational study, the rate of chromosome aberrations was significantly lower in subjects with high (28.4 mg/day) compared to low (20.5 mg/day) dietary niacin intake (39).

Upper digestive tract

  • Generally, relationships between dietary factors and cancer are established first in epidemiological studies and followed up by basic cancer research at the cellular level. In the case of niacin, research on biochemical and cellular aspects of DNA repair has stimulated an interest in the relationship between niacin intake and cancer risk in human populations (40). A large case-control study found increased consumption of niacin, along with antioxidant nutrients, to be associated with decreased incidence of oral (mouth), pharyngeal (throat), and esophageal cancers in northern Italy and Switzerland (41, 42). An increase in daily niacin intake of 6.2 mg was associated with about a 40% decrease in cases of cancers of the mouth and throat, while a 5.2 mg increase in daily niacin intake was associated with a similar decrease in cases of esophageal cancer.

Skin

  • Niacin deficiency can lead to severe sunlight sensitivity in exposed skin. Given the implication of NAD-dependent enzymes in DNA repair, there has been some interest in the effect of niacin on skin health. In vitro and animal experiments have helped gather information, but human data on niacin/NAD status and skin cancer are severely limited. One study reported that niacin supplementation decreased the risk of ultraviolet light (UV)-induced skin cancers in mice, despite the fact that mice convert tryptophan to NAD more efficiently than rats and humans and thus do not get severely deficient (43).
  • Hyper-proliferation and impaired differentiation of skin cells can alter the integrity of the skin barrier and increase the occurrence of pre-malignant and malignant skin conditions. A protective effect of niacin was suggested by topical application of myristyl nicotinate, a niacin derivative, which successfully increased the expression of epidermal differentiation markers in subjects with photodamaged skin (44). The activation of the “niacin receptors,” GPR109A and GPR109B, by pharmacologic doses of niacin could be involved in improving skin barrier function. Conversely, differentiation defects in skin cancer cells were linked to the abnormal cellular localization of defective “niacin receptors” (45).
  • Nicotinamide restriction with subsequent depletion of cellular NAD was shown to increase oxidative stress-induced DNA damage in a precancerous skin cell model, implying a protective role of NAD-dependent pathways in cancer (46). Altered NAD availability also affects sirtuin expression and activity in UV-exposed human skin cells. Along with PARPs, NAD-consuming sirtuins could play an important role in the cellular response to photodamage and skin homeostasis (47).

Type 1 diabetes mellitus

  • Type 1 (insulin-dependent) diabetes mellitus in children is known to result from the autoimmune destruction of insulin-secreting β-cells in the pancreas. Prior to the onset of symptomatic diabetes, specific antibodies, including islet cell antibodies (ICA), can be detected in the blood of high-risk individuals. The ability to detect individuals at high risk for the development of IDDM led to the enrollment of high-risk siblings of children with IDDM into trials designed to prevent its onset. Evidence from in vitro and animal research indicates that high levels of nicotinamide protect β-cells from damage by toxic chemicals, inflammatory white blood cells, and reactive oxygen species. Pharmacologic doses of nicotinamide (up to 3 grams/day) were first used to protect β-cells in patients shortly after the onset of IDDM.
  • An analysis of 10 published trials (5 placebo-controlled) found evidence of improved β-cell function after one year of treatment with nicotinamide, but the analysis failed to find any clinical evidence of improved glycemic (blood glucose) control (48). However, high doses of nicotinamide could decrease insulin sensitivity in high-risk relatives of IDDM patients (49), which might explain the finding of improved β-cell function without concomitant improvement in glycemic control.

http://lpi.oregonstate.edu/mic/vitamins/niacin

https://en.wikipedia.org/wiki/Tryptophan

https://www.technologyreview.com/s/534636/the-anti-aging-pill/

http://biochem.uiowa.edu/brenner/documents/bogan08.pdf

Elders with negative attitude about aging may be less resilient to stress

Older adults with a positive attitude about aging may be more resilient to stress, according to a new study.

“Previous research has generally found the same thing, a more positive attitude is beneficial,” said coauthor Jennifer Bellingtier, of North Carolina State University in Raleigh.

“People with positive attitudes are less likely to be hospitalized and tend to live longer,” she told Reuters Health.

The researchers had 43 adults, ages 60 to 96, answer questions about their experience with aging in general, like feeling more or less useful now than when they were younger, or more or less happy.

Then, on a daily basis for eight days, participants completed questionnaires that asked about stressful events and negative emotions like fear, irritability or distress.

As reported in The Journals of Gerontology: Series B, people with more positive attitudes about aging generally tended to report consistent emotional states across the eight-day period, regardless of stressors.

But among those with more negative attitudes, emotions fluctuated depending on their stressors.

For older adults, stress often centers on relations with family or friends, while for younger people it may more often be related to work, Bellingtier said.

Almost all cardiovascular functions tend to be worse in people with more negative reactions to stress, she said.

“The media presents a distorted view of aging, making jokes about mental and physical incompetence,” Bellingtier said. “The more you’re exposed to it the more you’re picking up those stereotypes.”

In fact, she said, older adults are often happier with their lives than people in their 20s or 30s, given their real world life experience and time to develop meaningful relationships.

She and her coauthors tried to account for personality in general as well, since people who are generally positive may have more positive attitudes about aging.

Becca Levy of the Yale School of Public Health in New Haven, Connecticut, has also studied this question, although she wasn’t part of this new study. She told Reuters Health by email that negative age stereotypes can exacerbate older individuals’ stress experience, while positive age stereotypes can buffer their experience of stress.

“In a recent intervention study with older individuals, we found that it is possible to bolster positive age stereotypes and reduce negative age stereotypes,” Levy said.

Can antidepressants cause neurodegenerative disease?

The following notes are compiled by Marcus William. Seek your doctor always.

Neurological disorders, neurological damages, and progressive neurological dysfunction are all possible side effects of antidepressant use.

And, in fact, acute neurological dysfunction is the standard and clinically desired outcome of antidepressant use, which begins with the first dose administered. Continued use may be considered “neurodegenerative” in some contexts or cases, but the degeneration may not always last beyond the treatment and withdrawal syndrome periods and does not constitute a disorder unto itself except as carved into specific subsets of symptoms.

Whether diseases considered independent entities, such as Parkinson’s, are within that scope of neurological side effects is not always agreed upon, because there may be differing causal factors (in terms of precipitating elements or mechanical functioning). So, while there are side effect clusters referred to by phrases like “Parkinsonian tremor”, “pseudo-Parkinsonism”, or “drug-induced Parkinsonism”, whether they are considered the ‘disease proper’ is sometimes more a matter of semantics than experience, symptomologically speaking.


Since we do not understand the origin of most neurodegenerative conditions, and the side effects of antidepressants can newly appear, or worsen, over the course of treatment, discontinuation, or post-use, differentiating between entities by citing the innately chronic or worsening nature of a disease not inherently attributed to drugging is not sufficient to distinguish drug-induced Parkinsonism from Parkinson’s that has no clear cause.

Some people do experience a reduction in neurological problems caused by antidepressants, after spending time off them and recovering, but it is not a guarantee, and withdrawal states or damages and dysfunction that persist or become more apparent post-discontinuation can give the appearance of a neurodegenerative process even if someone is essentially in a state of healing overall. And, of course, some changes or damages can lead to worsening problems, though the mechanics and outcomes are poorly studied, if studied at all.

Drug-induced Parkinsonian symptoms specifically have been seen to improve, continue, or worsen in respective groups of patients, meaning there is no predefined course in the short or long terms. Since antidepressants, and other psychotropics that are known to cause neurological side effects (including Parkinsonism in particular), can cause significant neuroplastic changes and are fundamentally neurotoxic, we cannot necessarily identify drug-induced states as non-degenerative or free from morphological alterations in trying to distinguish them from Parkinson’s as a primary condition.


Continuing with the example of Parkinson’s, drugs are considered the second leading cause of Parkinsonian symptoms, behind the greater and most probably heterogeneous category of “primary” Parkinson’s—an idiopathic presentation of symptoms and pathology without any perspicuous medical events being connected, eg drugging with psychotropics. So, even in that distinction we are dealing more with a semantic division than a practical one except that drug-induced Parkinsonism can diminish over time for some patients—that the underlying dysfunction seems to differ in at least some cases does not really get the patient anywhere.

Antidepressants are psychotropics, neurotoxins, and the source of dysfunctional changes on the physiological, biochemical, systemic, and epigenetic levels. This can give rise to new or worsening neurological conditions. Since we don’t understand the conditions we attempt to treat with antidepressants, don’t understand why they do what they do, and don’t understand primary neurological disorders in question, saying exactly what it is that people have when these side effects occur is far more speculative than simply pointing out that it does happen and it should be a consideration when weighing the risks and potential benefits of using antidepressants.


As for that article specifically, it presents information with a variety of potential implications for the increased rate of Parkinson’s seen in antidepressant users (not all of which were mentioned by the authors themselves):

Potential misclassifications

-Early undiagnosed Parkinson’s might involve depressive symptoms for some patients.

-Early undiagnosed Parkinson’s might involve symptoms misdiagnosed as depressive for some patients.

-Parkinson’s might be itself misdiagnosed at a higher rate in patients who have used antidepressants, perhaps at least partly due to their significant rate of neurological side effects (which include various movement disorders).

Potential connections

-Something(s) might be contributing to both Parkinson’s and depression, (or something diagnosed as depression).

-Depression might sometimes create or contribute to a potential for Parkinson’s.

-Drugs might create sometimes or create or contribute to a potential for Parkinson’s.

-Depression might sometimes worsen or exploit a latent potential for Parkinson’s.

-Drugs might sometimes worsen or exploit a latent potential for Parkinson’s.

We face a similar conundrum in dealing with other pharmaceutical neurotoxins, for example antipsychotics and methamphetamine, and the difficulties endemic to our low level of neurobiological and neuropathological understanding mean that we will probably not have definitive research about the roles such drugs play anytime soon.


Some References:

Drug-Induced Parkinsonism

Is 6 months of neuroleptic withdrawal sufficient to distinguish drug-induced parkinsonism from Parkinson’s disease?

[Drug-induced parkinsonism. Clinical aspects compared with Parkinson disease].

[Drug-induced parkinsonism].

http://www.sciencedirect.com/sci…

Understanding drug-induced parkinsonism

Methamphetamine and Parkinson’s Disease

 

Habits of highly effective brain by Alvaro Fernandez

Let’s review some good lifestyle options we can all follow to maintain, and improve, our vibrant brains.

  • 1. Learn more about the “It” in “Use It or Lose It“. A basic understanding will serve you well to appreciate your brain’s beauty as a living and constantly-developing dense forest with billions of neurons and synapses.
  • 2. Take care of your nutrition. Did you know that the brain only weighs 2% of body mass but consumesgood brain food over 20% of the oxygen and nutrients we intake? As a general rule, you don’t need expensive ultra-sophisticated nutritional supplements, just make sure you don’t stuff yourself with the “bad stuff”.
  • 3. Remember that the brain is part of the body. Things that exercise your body can also help sharpen your brain: physical exercise enhances neurogenesis, at any age!
  • 4. Practice positive, action-oriented thoughts until they become your default mindset and you look forward to creating something beautiful every new day. Too much stress and anxiety–either induced by external events or by your own thoughts–actually kills neurons and prevent the creation of new ones. physical exercise for brain health
  • 5. Thrive on Learning and Mental Challenges. The point of having a brain is precisely to learn and to adapt to challenging new environments. Once new neurons appear in your brain, where they migrate and how long they survive depends on how you use them. “Use It or Lose It” does not mean “do crossword puzzle number 1,234,567”. It means, “challenge your brain, and often, with novel activities”.
  • 6. We are (as far as we know) the only self-directed organisms in this planet. Aim high. Once you graduate from college, keep learning. Once you become too comfortable in one job, find a new one. The brain keeps developing ALWAYS, reflecting what you do with it.
  • 7. Explore, travel. Adapting to new locations forces you to pay more attention to your environment. Make new decisions, use your brain.
  • 8. Don’t Outsource Your Brain. Not to media personalities, not to politicians, not to your smart neighbour… Make your own decisions, and mistakes. That way, you are training your brain, not your neighbour’s.
  • 9. Develop and maintain stimulating friendships. We are social animals, and need social interaction. Which, by the way, is why ‘Baby Einstein’ or all those educational apps have been shown not to be the panacea for children development.
  • 10. Laugh. Often. Especially to cognitively complex humor, full of twists and surprises. Better, try to become the next Jon Stewart

Now, remember that what counts is not reading this article–or any other– but practicing a bit every day until small steps snowball into unstoppable, internalized habits…”cells that fire together wire together”…so, start improving one of these 10 habits today. Revisit the habit above that really grabbed your attention, and make a decision to try something different today and tomorrow.


Connie’s comments: As we learn to dance and instruct our limbs to move, we are growing neurons. Do take acidophilus capsules, eat pickled veggies and have a strong immune system to detox our brain (also with good sleep – take melatonin and calcium and magnesium when over 40 yrs of age). Powerful whole foods rich in sulfur and resveratrol and fish are good for our brain. Add coconut oil, walnut and avocado in your dish always.

Be happy and move often (be in the sun before 9am and after 5pm).

Pomegranates, red raspberries, strawberries and walnuts anti-aging molecule

pomen

Your gut bacteria and molecule in pomegranates , oak-aged red wine, red raspberries, strawberries and walnuts have anti-aging properties (anti Alzheimer’s and anti Parkinson’s).

Urolithins are microflora human metabolites of dietary ellagic acid derivatives[1] such as ellagitannins. They are produced in the human gut, and found in the urine in the form of urolithin B glucuronide after absorption of ellagitannins-containing food such as pomegranate,[2] strawberries, red raspberries, walnuts or oak-aged red wine.[3]

During intestinal metabolism by bacteria, ellagitannins and punicalagins are converted to urolithins, which have unknown biological activity in vivo in humans.[2][4] Urolithins metabolites of pomegranate juice ellagitannins localize specifically in the prostate gland, colon, and intestinal tissues of mice,[5] leading to clinical studies of pomegranate juice or fruit extracts for efficacy against several diseases.

Ellagitannins exhibit low bioavailability and are transformed in the gut to ellagic acid and its microbiota metabolites. Urolithins are found in plasma mostly as glucuronides at low concentrations.[6]

Urolithins production is dependent on the gut microbiome enterotype. Individuals producing urolithins show a much higher abundance of the Clostridium leptum group of Firmicutes phylum than Bacteroides or Prevotella.[7]

SW glitch in fMRI, brain scans faulty results

MRI SW glitch

A 90 yr old Alzheimer’s patient in a care home has rigid body and when moved by caregivers from her bed or wheel chair, they feel that she is a dead weight. She cannot move most of her limbs. Every day her daughter would massage her head and she still has appetite and loves to smile with open mouth and eyes whenever she sees me dancing in front of her.

There are many paths to healing. We can age like our mothers did or better if we know how to relax, get a massage, enjoy walks and dancing and more.

What if the fMRI scans has software glitch. We should always listen to our body, sleep and exercise more.

Lysosomes, anti-aging function

As the endpoint of endocytosis, the lysosome also acts as a safeguard in preventing pathogens from being able to reach the cytoplasm before being degraded. Pathogens often hijack endocytotic pathways such as pinocytosis in order to gain entry into the cell. The lysosome prevents easy entry into the cell by hydrolyzing the biomolecules of pathogens necessary for their replication strategies; reduced Lysosomal activity results in an increase in viral infectivity, including HIV.[18] In addition, AB5 toxins such as cholera hijack the endosomal pathway while evading lysosomal degradation.[18]

Disease

Lysosomes are responsible for a group of genetically inherited disorders called lysosomal storage diseases (LSD). They are a type of inborn errors of metabolism caused by malfunction of one of the enzymes. The rate of incidence is estimated to be 1 in 5,000 live births, and the true figure expected to be higher as many cases are likely to be undiagnosed or misdiagnosed. The primary cause is deficiency of an acidic hydrolase (a hydrolase which functions best in acidic environments). Other conditions are due to defects in lysosomal membrane proteins that fail to transport the enzyme, non-enzymatic soluble lysosomal proteins. The initial effect of such disorders is accumulation of specific macromolecules or monomeric compounds inside the endosomal–autophagic–lysosomal system.[4] This results in abnormal signaling pathways, calcium homeostasis, lipid biosynthesis and degradation and intracellular trafficking, ultimately leading to pathogenetic disorders. The organs most affected are brain, viscera, bone and cartilage.[19][20]

There is no direct medical treatment to cure LSDs.[21] The most common LSD is Gaucher’s disease, which is due to deficiency of the enzyme glucocerebrosidase. Consequently, the enzyme substrate, the fatty acid glucosylceramide accumulates, particularly in white blood cells, which in turn affects spleen, liver, kidneys, lungs, brain and bone marrow. The disease is characterized by bruises, fatigue, anaemia, low blood platelets, osteoporosis, and enlargement of the liver and spleen.[22][23]

Metachromatic leukodystrophy is another lysosomal storage disease that also affects sphingolipid metabolism.

Lysosomotropism

Weak bases with lipophilic properties accumulate in acidic intracellular compartments like lysosomes. While the plasma and lysosomal membranes are permeable for neutral and uncharged species of weak bases, the charged protonated species of weak bases do not permeate biomembranes and accumulate within lysosomes. The concentration within lysosomes may reach levels 100 to 1000 fold higher than extracellular concentrations. This phenomenon is called “lysosomotropism”[24] or “acid trapping”. The amount of accumulation of lysosomotropic compounds may be estimated using a cell-based mathematical model.[25]

A significant part of the clinically approved drugs are lipophilic weak bases with lysosomotropic properties. This explains a number of pharmacological properties of these drugs, such as high tissue-to-blood concentration gradients or long tissue elimination half-lifes; these properties have been found for drugs such as haloperidol,[26] levomepromazine,[27] and amantadine.[28] However, high tissue concentrations and long elimination half-lives are explained also by lipophilicity and absorption of drugs to fatty tissue structures. Important lysosomal enzymes, such as acid sphingomyelinase, may be inhibited by lysosomally accumulated drugs.[29][30] Such compounds are termed FIASMAs (functional inhibitor of acid sphingomyelinase)[31] and include for example fluoxetine, sertraline, or amitriptyline.

Ambroxol is a lysosomotropic drug of clinical use to treat conditions of productive cough for its mucolytic action. Ambroxol triggers the exocytosis of lysosomes via neutralization of lysosomal pH and calcium release from acidic calcium stores.[32] Presumably for this reason, Ambroxol was also found to improve cellular function in some disease of lysosomal origin such as Parkinson‘s or lysosomal storage disease.[33


Betaine HCL, helps stomach acid in breaking down food

Low hydrochloric acid is a potential cause of cancer and other immune and auto-immune conditions

Everyone, without exception, has cancer genes, “oncogenes,” circulating around the body. These cancer genes are normally kept in check by a healthy immune system, but in the case of cancer, the immune system can no longer suppress the cancer genes, which can then get out of control and multiply. The immune system responds by forming a tumor to contain the malignant cancer cells.

Chemotherapy may suppress cancer cells temporarily but also destroys the immune system, exposing the patient to a very wide range of additional diseases as well as additional types of cancer through immune-suppressed cancer gene expression.

If the “Th1” immune system is compromised or disabled, the “Th2” component of the immune system attempts to take over. Th2, not being equipped to function as Th1, perceives genuine body tissues as foreign invaders, attacking them as it would a bacterium or virus. Th1 suppression is also a root cause of auto-immune diseases such as allergies, celiac disease and arthritis.

How betaine HCl supplementation can bring valuable health benefits

Betaine hydrochloride (betaine HCl) increases the concentration of hydrochloric acid in the stomach relative to how much is taken before meals. This enables the stomach to much more completely dissolve and process foods right down to base nutrients, as well as produce methyl groups, an important element in preventing cancer and other diseases.

Taking betaine HCl before meals helps the stomach make optimum use of all dietary nutrients, also optimizing the immune system gut flora, without which, even with a healthy diet, many diseases including cancer can arise and propagate.

Note to vegetarians and vegans: Avoid betaine hydrochloride supplements that also contain pepsin, extracted from pig stomachs.

Sources:

http://www.naturalnews.com

http://scdlifestyle.com

Learn more: http://www.naturalnews.com/043014_betaine_hydrochloride_stomach_acid_improved_digestion.html#ixzz4D5x1pDMh