Calcium in our foods and bodies

calcium-3cal-2

The effects of calcium on human cells are specific, meaning that different types of cells respond in different ways. However, in certain circumstances, its action may be more general. Ca2+ ions are one of the most widespread second messengers used in signal transduction. They make their entrance into the cytoplasm either from outside the cell through the cell membrane via calcium channels (such as Calcium-binding proteins or voltage-gated calcium channels), or from some internal calcium storages such as the endoplasmic reticulum[3] and mitochondria. Levels of intracellular calcium are regulated by transport proteins that remove it from the cell. For example, the sodium-calcium exchanger uses energy from the electrochemical gradient of sodium by coupling the influx of sodium into cell (and down its concentration gradient) with the transport of calcium out of the cell. In addition, the plasma membrane Ca2+ ATPase (PMCA) obtains energy to pump calcium out of the cell by hydrolysing adenosine triphosphate (ATP). In neurons, voltage-dependent, calcium-selective ion channels are important for synaptic transmission through the release of neurotransmitters into the synaptic cleft by vesicle fusion of synaptic vesicles.

Calcium’s function in muscle contraction was found as early as 1882 by Ringer. Subsequent investigations were to reveal its role as a messenger about a century later. Because its action is interconnected with cAMP, they are called synarchic messengers. Calcium can bind to several different calcium-modulated proteins such as troponin-C (the first one to be identified) and calmodulin, proteins that are necessary for promoting contraction in muscle.

In the endothelial cells which line the inside of blood vessels, Ca2+ ions can regulate several signaling pathways which cause the smooth muscle surrounding blood vessels to relax.[citation needed] Some of these Ca2+-activated pathways include the stimulation of eNOS to produce nitric oxide, as well as the stimulation of Kca channels to efflux K+ and cause hyperpolarization of the cell membrane. Both nitric oxide and hyperpolarization cause the smooth muscle to relax in order to regulate the amount of tone in blood vessels.[7] However, dysfunction within these Ca2+-activated pathways can lead to an increase in tone caused by unregulated smooth muscle contraction. This type of dysfunction can be seen in cardiovascular diseases, hypertension, and diabetes.


Calcium: magnesium ratio is 60:40 and always taken with Vit C, Vit D3 and zinc and in afternoon while iron rich foods is eaten in the morning since calcium and iron cancels each other out.

Hypocalcemia and Sepsis

hypoHypocalcemia varies from an asymptomatic biochemical abnormality to a life-threatening disorder, depending on the duration, severity, and rapidity of development. Hypocalcemia is caused by loss of calcium from or insufficient entry of calcium into the circulation.

Hypoparathyroidism is the most common cause of hypocalcemia and often develops because of surgery in the central neck requiring radical resection of head and neck cancers. It develops in 1% to 2% of patients after total thyroidectomy.

The hypocalcemia may be transient, permanent, or intermittent, as with vitamin D deficiency during the winter. Autoimmune hypoparathyroidism is seen as an isolated defect or as part of polyglandular autoimmune syndrome type I in association with adrenal insufficiency and mucocutaneous candidiasis. Most of these patients have autoantibodies directed against the calcium-sensing receptor. Congenital causes of hypocalcemia include activating mutations of calcium-sensing receptor, which has reset the calcium–parathyroid hormone (PTH) relation to a lower serum calcium level. Mutations affecting intracellular processing of the pre-pro-PTH molecule are also described and lead to hypoparathyroidism, hypocalcemia, or both. Finally, some cases are associated with hypoplasia or aplasia of the parathyroid glands; the best known is DiGeorge syndrome.

Pseudohypoparathyroidism is a group of disorders with postreceptor resistance to PTH. One classic variant is Albright’s hereditary osteodystrophy, associated with low stature, round facies, short digits, and mental retardation. Hypomagnesemia induces PTH resistance and also affects PTH production. Severe hypermagnesemia (>6 mg/dL) can lead to hypocalcemia by inhibiting PTH secretion. Vitamin D deficiency leads to hypocalcemia when associated with decreased dietary calcium intake. The low calcium level stimulates PTH secretion (secondary hyperparathyroidism), leading to hypophosphatemia.

Rhabdomyolysis and tumor lysis syndrome cause loss of calcium from the circulation when large amounts of intracellular phos-phate are released and precipitate calcium in bone and extraskeletal tissues. A similar mechanism causes hypocalcemia with phosphate administration.

Acute pancreatitis precipitates calcium as a soap in the abdomen, causing hypocalcemia. Hungry bone syndrome is hypocalcemia after surgery for hyperparathyroidism (HPT) in patients with severe prolonged disease (secondary or tertiary HPT in renal failure). Serum calcium is rapidly deposited into the bone. Hungry bone syndrome is rarely seen after correction of longstanding metabolic acidosis or after thyroidectomy for hyperthyroidism.

Several medications (e.g., ethylenediaminetetraacetic acid [EDTA], citrate present in transfused blood, lactate, foscarnet) chelate calcium in the circulation, sometimes producing hypocalcemia in which ionized calcium is decreased, cohereas total calcium may be normal. Extensive osteoblastic skeletal metastases (prostate and breast cancers) may also cause hypocalcemia. Chemotherapy, including cisplatin, 5-fluorouracil, and leucovorin, causes hypocalcemia mediated through hypomagnesemia. Hypocalcemia after surgery can be mediated by the citrate content of transfused blood or by a large volume of fluid administration and hypoalbuminemia. Patients with sepsis demonstrate hypocalcemia usually associated with hypoalbuminemia.


Ionized means charged. Sepsis is the other cause of hypocalcemia (absence of PTH secretion or hypoparathyroidism). Low calcium, high magnesium and low Vitamin D3. Can also be congenital (mutations of CaSR, PTH, and parathyroid aplasia)


Supplementation of calcium 60%, magnesium 40% with zinc, Vitamin D and C and should be taken before eating food rich in iron since iron cancels calcium absorption.

Metabolic pathway provides cues for cancer, aging and health care

metabolic path.JPGIn biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes.[1] In a metabolic pathway, the product of one enzyme acts as the substrate for the next. These enzymes often require dietary minerals, vitamins, and other cofactors to function.

Different metabolic pathways function based on the position within a eukaryotic cell and the significance of the pathway in the given compartment of the cell.[2] For instance, the citric acid cycle, electron transport chain, and oxidative phosphorylation all take place in the mitochondrial membrane. In contrast, glycolysis, pentose phosphate pathway, and fatty acid biosynthesis all occur in the cytosolof a cell.[3]

There are two types of metabolic pathways that are characterized by their ability to either synthesize molecules with the utilization of energy (anabolic pathway) or break down of complex molecules by releasing energy in the process (catabolic pathway).[4] The two pathways complement each other in that the energy released from one is used up by the other. The degradative process of a catabolic pathway provides the energy required to conduct a biosynthesis of an anabolic pathway.[4] In addition to the two distinct metabolic pathways is the amphibolic pathway, which can be either catabolic or anabolic based on the need for or the availability of energy.[5]

Pathways are required for the maintenance of homeostasis within an organism and the flux of metabolites through a pathway is regulated depending on the needs of the cell and the availability of the substrate. The end product of a pathway may be used immediately, initiate another metabolic pathway or be stored for later use. The metabolism of a cell consists of an elaborate network of interconnected pathways that enable the synthesis and breakdown of molecules (anabolism and catabolism)

Glycolysis, Oxidative Decarboxylation of Pyruvate, and Tricarboxylic Acid (TCA) Cycle

Net reactions of common metabolic pathways

Each metabolic pathway consists of a series of biochemical reactions that are connected by their intermediates: the products of one reaction are the substrates for subsequent reactions, and so on. Metabolic pathways are often considered to flow in one direction. Although all chemical reactions are technically reversible, conditions in the cell are often such that it is thermodynamically more favorable for flux to flow in one direction of a reaction. For example, one pathway may be responsible for the synthesis of a particular amino acid, but the breakdown of that amino acid may occur via a separate and distinct pathway. One example of an exception to this “rule” is the metabolism of glucose. Glycolysis results in the breakdown of glucose, but several reactions in the glycolysis pathway are reversible and participate in the re-synthesis of glucose (gluconeogenesis).

  • Glycolysis was the first metabolic pathway discovered:
  1. As glucose enters a cell, it is immediately phosphorylated by ATP to glucose 6-phosphate in the irreversible first step.

  2. In times of excess lipid or protein energy sources, certain reactions in the glycolysis pathway may run in reverse in order to produce glucose 6-phosphate which is then used for storage as glycogen or starch.

  • Metabolic pathways are often regulated by feedback inhibition.
  • Some metabolic pathways flow in a ‘cycle’ wherein each component of the cycle is a substrate for the subsequent reaction in the cycle, such as in the Krebs Cycle (see below).
  • Anabolic and catabolic pathways in eukaryotes often occur independently of each other, separated either physically by compartmentalization within organelles or separated biochemically by the requirement of different enzymes and co-factors.

Catabolic pathway (catabolism)

A catabolic pathway is a series of reactions that bring about a net release of energy in the form of a high energy phosphate bond formed with the energy carriers Adenosine Diphosphate (ADP) and Guanosine Diphosphate (GDP) to produce Adenosine Triphosphate (ATP) and Guanosine Triphosphate (GTP), respectively. The net reaction is, therefore, thermodynamically favorable, for it results in a lower free energy for the final products.[6] A catabolic pathway is an exergonic system that produces chemical energy in the form of ATP, GTP, NADH, NADPH, FADH2, etc. from energy containing sources such as carbohydrates, fats, and proteins. The end products are often carbon dioxide, water, and ammonia. Coupled with an endergonic reaction of anabolism, the cell can synthesize new macromolecules using the original precursors of the anabolic pathway.[7] An example of a coupled reaction is the phosphorylation of fructose-6-phosphate to form the intermediate fructose-1,6-bisphosphate by the enzyme phsophofructokinase accompanied by the hydrolysis of ATP in the pathway of glycolysis. The resulting chemical reaction within the metabolic pathway is highly thermodynamically favorable and, as a result, irreversible in the cell.[8]

{\displaystyle Fructose-6-Phosphate+ATP\longrightarrow Fructose-1,6-Bisphosphate+ADP}{\displaystyle Fructose-6-Phosphate+ATP\longrightarrow Fructose-1,6-Bisphosphate+ADP}

Cellular respiration

Main article: Cellular respiration

A core set of energy-producing catabolic pathways occur within all living organisms in some form. These pathways transfer the energy released by breakdown of nutrients into ATP and other small molecules used for energy (e.g. GTP, NADPH, FADH). All cells can perform anaerobic respirationby glycolysis. Additionally, most organisms can perform more efficient aerobic respiration through the citric acid cycle and oxidative phosphorylation. Additionally plants, algae and cyanobacteria are able to use sunlight to anabolically synthesize compounds from non-living matter by photosynthesis.

Gluconeogenesis Mechanism

Anabolic pathway (anabolism)

In contrast to catabolic pathways, are the anabolic pathways that require an input of energy in order to conduct the construction of macromolecules such as polypeptides, nucleic acids, proteins, polysaccharides, and lipids. The isolated reaction of anabolism is unfavorable in a cell due to a positive Gibbs Free Energy (+ΔG); thus, an input of chemical energy through a coupling with an exergonic reaction is necessary.[9] The coupled reaction of the catabolic pathway affects the thermodynamics of the reaction by lowering the overall activation energy of an anabolic pathway and allowing the reaction to take place.[10] Otherwise, an endergonic reaction is non-spontaneous.

An anabolic pathway is a biosynthetic pathway, meaning that it combines smaller molecules to form larger and more complex ones.[11] An example is the reversed pathway of glycolysis, otherwise known as gluconeogenesis, which occurs in the liver and sometimes in the kidney in order to maintain proper glucose concentration in the blood and to be able to supply the brain and muscle tissues with adequate amount of glucose. Although gluconeogenesis is similar to the reverse pathway of glycolysis, it contains three distinct enzymes from glycolysis that allow the pathway to occur spontaneously.[12] An example of the pathway for gluconeogenesis is illustrated in the image titled “Gluconeogenesis Mechanism“.

 

Changes in mineral metabolism in chronic kidney disease, an ebook

Abstract

With progression of chronic kidney disease (CKD), disorders of mineral metabolism appear. The classic sequence of events begins with a deficit of calcitriol synthesis and retention of phosphorus. As a result of this, serum calcium decreases and parathyroid hormone (PTH) is stimulated, producing in the bone the high turnover (HT) bone disease known as osteitis fibrosa while on the other extreme we find the forms of low turnover (LT) bone disease.

Initially associated with aluminum intoxication, these diseases are now seen primarily in older and/or diabetic patients, who in a uremic setting have relatively low levels of PTH to maintain normal bone turnover.

Osteomalacia is also included in this group, which after the disappearance of aluminum intoxication is rarely observed. LT forms of hyperparathyroidism facilitate the exit of calcium (Ca) and phosphorus (P) from bone, whereas the adynamic bone limits the incorporation of Ca and P into bone tissue.

Therefore, both forms facilitate the availability of Ca and P, which ends up being deposited in soft tissues such as arteries. The link between bone disease and vascular calcifications in CKD is now a well-established phenomenon.

Diagnostic strategies Calcium, Phosphorus

They have little capacity to predict underlying bone disease, but their regular measurement is decisive for therapeutic management of the patient, especially in the dose titration stages of intestinal phosphorus binders, vitamin D analogs or calcimimetics. Ideally, Ca++ should be used, but total Ca is routinely used. It is recommended to adjust albumin levels in the event of hypoalbuminemia (for each g/dL of decrease in albumin, total serum Ca decreases 0.9 mg/dL). The following formula facilitates rapid calculation of corrected total calcium: Corrected total Ca (mg/dL) = total Ca (mg/dL) + 0.8 [4-albumina (g/dL)]. Parathyroid hormone “Intact” PTH is the biochemical parameter that best correlates with bone histology (levels measured with the Allegro assay from Nichols Institute Diagnostics, no longer available).

Various assays are currently available that use antibodies against different fragments of the molecule, but they have significant intermethod variability and have not been validated. A whole PT assay (1-84) is currently unavailable. A consensus to establish uniform criteria for PTH measurement remains to be established. During the dose titration stages of intestinal phosphorus binders, vitamin D analogs or calcimimetics, more frequent measurement may be required based on clinical judgment.

Calcifediol (25(OH) D3 )

It is important to maintain adequate levels of 25(OH)D3 (> 30 ng/mL), since they will be the substrate for production of 1- 25(OH)2 D3, and their deficiency aggravates hyperthyroidism. Determining 25(OH)D3 levels every 6-12 months is a recommended guideline.

Other markers of bone turnover (osteocalcin, total and bone alkaline phosphate, free pyridolines in serum, and C-terminal telopeptide of collagen) do not improve the predictive power of PTH and therefore their systematic use is not justified.

Radiologic studies Radiologic studies are of little diagnostic utility, because biochemical changes precede radiologic changes. Systematic radiologic evaluation of the skeleton in asymptomatic patients is not justified at present. They are useful as the first step in the study to detect vascular calcifications and amyloidosis due to b2-microglobulin and in symptomatic and at risk patients to detect vertebral fractures.

Bone densitometry

Dual energy x-ray absorptiometry (DEXA) is the standard method to determine bone mineral density (usually in the femoral neck and vertebrae). It provides information on changes in bone mineral content, but not on the type of underlying bone disease. It is useful for follow-up of bone mass or for the study of bone mass changes in the same patient. Its value as a predictor of the risk of fracture has not been demonstrated in patients on kidney replacement therapy or with advanced chronic kidney disease. It is indicated in patients with fractures or risk factors for osteoporosis. Bone biopsy: The “gold standard” for diagnosis of bone disease. With improved knowledge of the value of noninvasive parameters, its use is infrequent.

Diet

The recommended diet for the patient with CKD is traditionally based on protein restriction and phosphorus restriction for control of mineral metabolism. A favorable circumstance is that there is a close relationship between protein and phosphorus intake. In CKD stages 3, 4 and 5, it is recommended to restrict phosphorus intake to between 0.8-1 g/day when serum levels of phosphorus and PTH are above the recommended range. This is approximately equivalent to a diet of 50-60 g of protein. This reasonable antiproteinuric strategy that also restricts phosphorus intake is nutritionally safe. What should we tell them to eat? In a practical and oversimplified way, we recommend the following daily intake: Animal proteins: 1 serving (100-120 g), dairy products: 1 serving (equivalent to 200-240 mL of milk or 2 yoghourts), bread, cereals, pastas (1 cup of pasta, rice or legumes + some bread or cookies), vegetables and fruits relatively freely, but with moderation. 4.2. Medication Vitamin D supplements should be provided if serum levels are less than 30 ng/mL. In Spain, vitamin D3 (cholecalciferol) is marketed as Vitamin D3 Berenguer 2,000 IU/mL of solution. Combinations of calcium with cholecalciferol are also available. Most of the dosage forms contain approximately 500 mg of Ca+ and 400 IU of cholecalciferol.

https://www.ncbi.nlm.nih.gov/pubmed/19018742

Neck pain and MTHFR gene , folate , methionine

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My co-worker complained of chronic neck pain and her doctor prescribed a med and an iron pill. My mom uses Zyflamend in evening (with calcium and magnesium supplement in 60:40 ratio with Vit D, zinc and C) and iron rich food for lunch and avoided inflammatory foods such as red meat and eggplant.  I suggested a massage stroke (using the thumb in one downward motion from neck to back) and oil mixed with eucalyptus, tea tea oil and apricot oil.  A Fluradix liquid iron supplement with whole foods in the morning will also help, including raisins,liver,dark chocolate and blackstrap mollases.  A chronic pain is indicative of a deep rooted health issue that must be addressed at the core. There genes that affect how we absorb iron. Vit C rich foods and vinegar help in the absorption of iron (eaten in the morning and noon) and calcium (eaten in the evening because iron and calcium cancels each other).  I will always add probiotics and prebiotics in this health issue.

  1. Avoid taking folic acid blocking or depleting drugs, such as birth control pills or Methyltrexate
  2. Avoid taking proton pump inhibitors, like Prilosec or Prevacid or antacids, like Tums, which may block essential Vitamin B12 absorption
  3. Have your homocysteine measured, which if elevated may indicate a problem with methylation or a deficiency of B12 or folate.  If your homocysteine is elevated, limit your intake ofmethionine-rich foods
  4. Avoid eating processed foods, many of which have added synthetic folic acid.  Instead eat whole foods with no added chemicals or preservatives.
  5. Get your daily intake of leafy greens, like spinach, kale, swiss chard or arugula, which are loaded with natural levels of folate that your body can more easily process.
  6. Eat hormone-free, grass-fed beef, organic pastured butter or ghee, and eggs from free-range, non-GMO fed chickens.
  7. Remove any mercury amalgams with a trained biologic dentist.  Avoid aluminum exposure in antiperspirants or cookware.  Avoiding heavy metal or other toxic exposure is important.
  8. Make sure you supplementing with essential nutrients, like methyl-B12, methyl-folate, TMG, N-acetylcysteine, riboflavin, curcumin, fish oil, Vitamins C, D, E, and probiotics.  If you are double homozygous for MTHFR mutations, you should proceed very cautiously with methyl-B12 and methyl-folate supplementation as some people do not tolerate high doses.  Introduce nutrients one by one and watching for any adverse reactions.  Use extreme caution when supplementing with niacin, which can dampen methylation.
  9. Make time for gentle detox regimens several times per week.  These could include infrared sauna, epsom salt baths, dry skin brushing, and regular exercise or sweating.

See MTHFR gene mutation, iron and neck pain

methio 4.JPG

Cancer fighting diet

 

parsleycilantrosulfur-richyellowgreens.JPGWith regards to a cancer treatment, every food that we eat or drink can be categorized into several different categories:

  • Foods that feed and strengthen the cancer cells and/or the microbes in the cancer cells and body. Examples would be: refined sugar (e.g. see: Challenge Cancer Website), refined flour, soda pop, dairy products, etc.
  • Foods that cause cancer (e.g. trans fatty acids [margarine, french fries and virtually every other processed food you buy], aspartame [Diet Coke, NutraSweet, Equal, etc.], MSG, polyunsaturated oils [e.g. corn oil], etc.)
  • Foods that directly interfere with alternative treatments for cancer (e.g. chlorine, fluoride, alcohol, coffee, etc.)
  • Foods that occupy and distract the immune system from focusing on killing the cancer cells (e.g. beef, turkey, etc.)
  • Foods that contain nutrients that kill the cancer cells, stop the spread of cancer, or in some other way help treat the cancer (e.g. purple grapes with seeds and skin, red raspberries with seeds, strawberries with seeds, broccoli, cauliflower, several herbs, carrots, pineapples, almonds, etc.)

Cooking destroys the enzymes in the vegetables and make them far less digestible and far less effective in treating cancer. Pasteurizing any food or drink also does this.

Read More http://www.cancertutor.com/alt_diet/

Oxalic acid in whole foods is deadly to cancer cells

50% of the foods a cancer patients eats should have high oxalic acid content.

Oxalic Acid Foods List: Carrot juice, with a little beet juice, is a common cancer treatment. Both foods are high in oxalic acid.  Note: Cooked your greens (steamed, do not over cook) and eat calcium-rich whole foods.

Foods High in Oxalic Acid

High levels of oxalic acid can have harmful effects on the body. When the concentration of oxalic acid in the body increases, it precipitates out as crystals, that irritate the body tissues, and can get lodged in the kidneys and bladder as ‘stones’. When the acid combines with minerals like calcium, it forms an interlocking compound that destroys the nutritional value of both, resulting in deficiency of the minerals.

Vegetables

There are several vegetables containing high amount of oxalic acid and should be cooked well (not eaten raw) for people with recurrent kidney stones or other such conditions. The United States Department of Agriculture has ranked parsley, highest in oxalic acid content, as it contains about 1.70g of oxalic acid per 100g.

  • Beets
  • Sweet potatoes
  • Celery
  • Dandelion greens
  • Eggplant
  • Kale
  • Chives
  • Broccoli
  • Carrots
  • Green Pepper
  • Parsnips
  • Potatoes
  • Pumpkin
  • Spinach
  • Squash
  • Turnip greens
  • Watercress
  • Okra
  • Collards
  • Escarole
  • Leeks
  • Purslane
  • Radish
  • Cassava

Fruits

Certain fruits have a high oxalic acid content. They are as follows:

  • Concord grapes
  • Kiwi
  • Lemon peel
  • Figs
  • Blueberries
  • Raspberries
  • Plums
  • Tangerines
  • Starfruit
  •  Nuts and Seeds

  • Peanuts
  • Almonds
  • Hazel nuts
  • Brazil nuts
  • Pecans
  • Sesame seeds
  • Poppy Seeds
  • Sunflower seeds
  • Cashews
  • Legumes and Grains

Majority of legumes are rich in oxalic acid. Some of them are as follows:

  • Black beans
  • Kidney beans
  • Garbanzo beans
  • Lima beans
  • Brussels sprouts
  • Whole wheat
  • Oatmeal
  • Buckwheat
  • Amaranth
  •  Other Foods

Oxalic acid is mainly present in plant products. A lot of spices and condiments also contain a considerable amount of oxalic acid. Tea leaves are known to contain among the highest measured concentration of the acid. However, as only a small amount of leaves are used for brewing, the content of the acid in many tea beverages is quite low. Here are some other foods containing it:

  • Cinnamon
  • Ginger
  • Lettuce
  • Soy products
  • Chocolate
  • Cocoa
  • Tea
  • Beer

Increase the amount of calcium/magnesium (60:40 ratio) in your diet, avoiding processed and pasteurized food.

Low amounts of calcium in your diet will increase your chances of forming calcium oxalate kidney stones. Many people are afraid to eat calcium because of the name “calcium oxalate stones.” However, calcium binds oxalate in the intestines. A diet rich in calcium helps reduce the amount of oxalate being absorbed by your body, so stones are less likely to form. Eat calcium rich foods and beverages every day (2 to 3 servings) from dairy foods or other calcium-rich foods.

Also, eating high calcium foods at the same time as high oxalate food is helpful; for example have low fat cheese with a spinach salad or yogurt with berries. If you take a calcium supplement, calcium citrate is the preferred form.

Limit Vitamin C content of your diet.

Oxalate is produced as an end product of Vitamin C (ascorbic acid) metabolism. Large doses of Vitamin C may increase the amount of oxalate in your urine, increasing the risk of kidney stone formation. If you are taking a supplement, do not take more than 500 mg of Vitamin C daily.

Drink the right amount of fluids every day.

It is very important to drink plenty of liquids. Your goal should be 10-12 glasses a day. At least 5-6 glasses should be water. You may also want to consider drinking lemonade. Research suggests that lemonade may be helpful in reducing the risk of calcium oxalate stone formation.

Eating the right amount of protein daily.

Eating large amounts of protein may increase the risk of kidney stone formation. Your daily protein needs can usually be met with 2-3 servings a day, or 4 to 6 ounces. Eating more than this if you are at risk at kidney stones is unnecessary.

Reduce the amount of sodium in your diet. Eat seaweeds.

Depression is a brain disease

In a genome-wide study, Perlis and colleagues found 17 genetic variations linked to depression at 15 genome locations. In addition to hinting at a link between depression and brain gene expression during development, there was also evidence of overlap between the genetic basis of depression and other mental illnesses. While the genome sites identified still account for only a fraction of the risk for depression, the researchers say the results support the strategy of complementing more traditional methods with crowd-sourced data.

To increase their odds of detecting these weak genetic signals, the researchers adopted a strategy of studying much larger samples than had been used in the earlier genome-wide studies. They first analyzed common genetic variation in 75,607 people of European ancestry who self-reported being diagnosed or treated for depression and 231,747 healthy controls of similar ethnicity. These data had been shared by people who purchased their own genetic profiles via the 23 and Me website and agreed to participate in the company’s optional research initiative, which makes data available to the scientific community, while protecting privacy.

The researchers integrated these data with results from a prior Psychiatric Genomic Consortium  genome-wide-association study, based on clinician-vetted diagnoses of more than 20,000 patients and controls of European ancestry. They then followed-up with a closer look at certain statistically suspect sites from that analysis in an independent 23 and Me “replication” sample of 45,773 cases and 106,354 controls.

“We hope these findings help people understand that depression is a brain disease, with it’s own biology,” said Perlis. “Now comes the hard work of using these new insights to try to develop better treatments.”

Hyde CL, Nagle MW, Tian C, Chen X, Paciga SA, Wendland JR, Tung J, Hinds DA, Perlis RH, Winslow AR. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature Genetics, Aug 1., 2016. doi:10.1038/ng.3623

About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

Five Major mental disorders share genetic roots

Prior to the study, researchers had turned up evidence of shared genetic risk factors for pairs of disorders, such as schizophenia and bipolar disorder, autism and schizophrenia and depression and bipolar disorder. Such evidence of overlap at the genetic level has blurred the boundaries of traditional diagnostic categories and given rise to research domain criteria, or RDoC, an NIMH initiative to develop new ways of classifying psychopathology for research based on neuroscience and genetics as well as observed behavior.

To learn more, the consortium researchers analyzed the five key disorders as if they were the same illness. They screened for evidence of illness-associated genetic variation across the genomes of 33,332 patients with all five disorders and 27,888 controls, drawing on samples from previous consortium mega-analyses.

For the first time, specific variations significantly associated with all five disorders were among several suspect genomic sites that turned up. These included variation in two genes that code for the cellular machinery for regulating the flow of calcium into neurons. Variation in one of these, called CACNA1C, which had previously been implicated in susceptibility to bipolar disorder, schizophrenia and major depression, is known to impact brain circuitry involved in emotion, thinking, attention and memory – functions disrupted in mental illnesses. Variation in another calcium channel gene, called CACNB2, was also linked to the disorders.

Alterations in calcium-channel signaling could represent a fundamental mechanism contributing to a broad vulnerability to psychopathology, suggest the researchers.

They also discovered illness-linked variation for all five disorders in certain regions of chromosomes 3 and 10. Each of these sites spans several genes, and the specific causal factors within them remain elusive. However, one region, called 3p21, which produced the strongest signal of illness association, harbors suspect variations identified in previous genome-wide studies of bipolar disorder and schizophrenia.

Source: Jordan Smoller, M.D., Massachusetts General Hospital

CACNA1c 3CACNA1C 2CACNA1 1

References

Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. The Lancet, February 28, 2013

 

CACNA1C,

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