Coffee and magnesium levels

Symptoms of poor magnesium intake can include muscle cramps, facial tics, poor sleep, and chronic pain. It pays to ensure that you get adequate magnesium before signs of deficiency occur.

But how can you know whether you’re getting enough?

According to population studies of average magnesium intake, there’s a good chance that you’re not.

Less than 30% of U.S. adults consume the Recommended Daily Allowance (RDA) of magnesium. And nearly 20% get only half of the magnesium they need daily to remain healthy.1 2 3

magnesium rda intake

Estimated U.S. Intake of Magnesium Recommended Daily Allowance


One method of assessing your magnesium status is to simply contact your health care provider and request detailed magnesium testing. Yet magnesium assessment is typically done using blood serum testing, and these tests can be misleading. Only 1% of magnesium in the body is actually found in blood, and only .3% is found in blood serum, so clinical blood serum testing may not successfully identify magnesium deficiency.

What to do?

Fortunately, it’s possible to get a sense of where your intake may lie simply by asking yourself a few questions about your lifestyle, and watching for certain signs and signals of low magnesium levels.

Learn how to read your signs below, and find out what you can do to ensure magnesium balance and good health. If you answer yes to any of the following questions, you may be at risk for low magnesium intake.

1. Do you drink carbonated beverages on a regular basis?

Most dark colored sodas contain phosphates. These substances actually bind with magnesium inside the digestive tract, rendering it unavailable to the body. So even if you are eating a balanced diet, by drinking soda with your meals you are flushing magnesium out of your system.4 5 6

The average consumption of carbonated beverages today is more than ten times what it was in 1940.7This skyrocketing increase is responsible for both reduced magnesium and calcium availability in the body.8 9

2. Do you regularly eat pastries, cakes, desserts, candies or other sweet foods?

sugar and magnesium depletion

Refined sugar is not only a zero magnesium product but it also causes the body to excrete magnesium through the kidneys. The process of producing refined sugar from sugar cane removes molasses, stripping the magnesium content entirely.

And sugar does not simply serve to reduce magnesium levels. Sweet foods are known by nutritionists as “anti-nutrients”. Anti-nutrients like sweets are foods that replace whole nutritious foods in the diet, yet actually consume nutrients when digested, resulting in a net loss. Because all foods require vitamins and minerals to be consumed in order to power the process of digestion, it’s important to choose foods that “put back” vital nutrients, and then some.

The more sweet foods and processed baked goods you have in your diet, the more likely you are deficient in magnesium and other vital nutrients.

3. Do you experience a lot of stress in your life, or have you recently had a major medical procedure such as surgery?

Both physical and emotional stress can be a cause of magnesium deficiency.

Stress can be a cause of magnesium deficiency, and a lack of magnesium tends to magnify the stress reaction, worsening the problem. In studies, adrenaline and cortisol, byproducts of the “fight or flight” reaction associated with stress and anxiety, were associated with decreased magnesium.4

Because stressful conditions require more magnesium use by the body, all such conditions may lead to deficiency, including both psychological and physical forms of stress such as surgery, burns, and chronic disease.

4. Do you drink coffee, tea, or other caffeinated drinks daily?

coffee and magnesium loss

Magnesium levels are controlled in the body in large part by the kidneys, which filter and excrete excess magnesium and other minerals. But caffeine causes the kidneys to release extra magnesium regardless of body status.

If you drink caffeinated beverages such as coffee, tea and soda regularly, your risk for magnesium deficiency is increased.

5. Do you take a diuretic, heart medication, asthma medication, birth control pills or estrogen replacement therapy?

The effects of certain drugs have been shown to reduce magnesium levels in the body by increasing magnesium loss through excretion by the kidneys.

6. Do you drink more than seven alcoholic beverages per week?

alcohol and magnesium depletion

The effect of alcohol on magnesium levels is similar to the effect of diuretics: it lowers magnesium available to the cells by increasing the excretion of magnesium by the kidneys. In studies, clinical magnesium deficiency was found in 30% of alcoholics.10

Increased alcohol intake also contributes to decreased efficiency of the digestive system, as well as Vitamin D deficiency, both of which can contribute to low magnesium levels.11

7. Do you take calcium supplements without magnesium or calcium supplements with magnesium in less than a 1:1 ratio?

Studies have shown that when magnesium intake is low, calcium supplementation may reduce magnesium absorption and retention.12 13 14 And, whereas calcium supplementation can have negative effects on magnesium levels, magnesium supplementation actually improves the body’s use of calcium.7

calcium and magnesium absorption

Though many reports suggest taking calcium to magnesium in a 2:1 ratio, this figure is largely arbitrary. The ideal ratio for any individual will vary depending on current conditions as well as risk factors for deficiency.

However, several researchers now support a 1:1 calcium to magnesium ratio for improved bone support and reduced risk of disease. This is due not only to the increased evidence pointing to widespread magnesium deficiency, but also concerns over the risk of arterial calcification when low magnesium stores are coupled with high calcium intake.

According to noted magnesium researcher Mildred Seelig:

The body tends to retain calcium when in a magnesium-deficient state. Extra calcium intake at such a time could cause an abnormal rise of calcium levels inside the cells, including the cells of the heart and blood vessels… Given the delicate balance necessary between calcium and magnesium in the cells, it is best to be sure magnesium is adequate if you are taking calcium supplements.”8

8. Do you experience any of the following:

  • Anxiety?
  • Times of hyperactivity?
  • Difficulty getting to sleep?
  • Difficulty staying asleep?

The above symptoms may be neurological signs of magnesium deficiency. Adequate magnesium is necessary for nerve conduction and is also associated with electrolyte imbalances that affect the nervous system. Low magnesium is also associated with personality changes and sometimes depression.

9. Do you experience any of the following:

  • Painful muscle spasms?
  • Muscle cramping?
  • Fibromyalgia?
  • Facial tics?
  • Eye twitches, or involuntary eye movements?

Neuromuscular symptoms such as these are among the classic signs of a potential magnesium deficit.

Without magnesium, our muscles would be in a constant state of contraction.

Magnesium is a required element of muscle relaxation, and without it our muscles would be in a constant state of contraction. Calcium, on the other hand, signals muscles to contract. As noted in the book The Magnesium Factor, the two minerals are “two sides of a physiological coin; they have actions that oppose one another, yet they function as a team.”8

Chvostek’s Sign and Trousseau’s Sign are both clinical tests for involuntary muscle movements, and both may indicate either calcium or magnesium deficiency, or both. In fact, magnesium deficiency may actually appear as calcium deficiency in testing, and one of the first recommendations upon receiving low calcium test results is magnesium supplementation.

10. Did you answer yes to any of the above questions and are also age 55 or older?

Older adults are particularly vulnerable to low magnesium status. It has been shown that aging, stress and disease all contribute to increasing magnesium needs, yet most older adults actually take in less magnesium from food sources than when they were younger.

In addition, magnesium metabolism may be less efficient as we grow older, as changes the GI tract and kidneys contribute to older adults absorbing less and retaining less magnesium.15

If you are above 55 and also showing lifestyle signs or symptoms related to low magnesium, it’s particularly important that you work to improve your magnesium intake. When body stores of magnesium run low, risks of overt hypomagnesaemia (magnesium deficiency) increase significantly.


Magnesium’s impact is so crucial and far reaching that symptoms of its absence reverberate throughout the body’s systems. This makes signs of its absence hard to pin down with absolute precision, even for cutting edge researchers.  Doctors Pilar Aranda and Elena Planells noted this difficulty in their report at the International Magnesium Symposium of 2007:

The clinical manifestations of magnesium deficiency are difficult to define because depletion of this cation is associated with considerable abnormalities in the metabolism of many elements and enzymes. If prolonged, insufficient magnesium intake may be responsible for symptoms attributed to other causes, or whose causes are unknown.”

Among researchers, magnesium deficiency is known as the silent epidemic of our times, and it is widely acknowledged that definitive testing for deficiency remains elusive. Judy Driskell, Professor, Nutrition and Health Sciences at the University of Nebraska, refers to this “invisible deficiency” as chronic latent magnesium deficiency, and explains:

Normal serum and plasma magnesium concentrations have been found in individuals with low magnesium in [red blood cells] and tissues. Yet efforts to find an indicator of subclinical magnesium status have not yielded a cost-effective one that has been well validated.”16

Yet while the identification of magnesium deficiency may be unclear, its importance is undeniable.

Magnesium activates over 300 enzyme reactions in the body, translating to thousands of biochemical reactions happening on a constant basis daily. Magnesium is crucial to nerve transmission, muscle contraction, blood coagulation, energy production, nutrient metabolism and bone and cell formation.

Considering these varied and all-encompassing effects, not to mention the cascading effect magnesium levels have on other important minerals such as calcium and potassium, one thing is clear – long term low magnesium intake is something to be avoided.

Connie’s comments: I sometimes drink decaf coffee before I exercise and eat in the morning. I take 60:40 calcium:magnesium with Vitamin D and C in the afternoon and at night. And always choose whole foods rich in magnesium since I have difficulty sleeping and relieve muscle pain.

Email for supplements personalized to your body composition. I get my supplements at Life Extension and I am a wholesaler.

Decreased bone mineral density (BMD) leads to increased risk of cardiovascular (CV) disease

A study to optimise bone strength and reducing risk of fracture, while at the same time decreasing risk of cardiovascular disease was done by the following team:

1Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, USA
2Cleveland Clinic Foundation, Center for Functional Medicine, Cleveland, Ohio, USA
3Center for Primary Health Care Research, Department of Clinical Sciences, Faculty of Medicine at Lund University, Malmö, Sweden
4Emeritus Professor of Nutritional Science, Colorado State University, Fort Collins, Colorado, USA
Correspondence to Dr James H O’Keefe; gro.sekul-tnias@efeekoj

The majority of Americans do not consume the current recommended dietary allowance for calcium, and the lifetime risk of osteoporosis is about 50%. However, traditional mononutrient calcium supplements may not be ideal. We comprehensively and systematically reviewed the scientific literature in order to determine the optimal dietary strategies and nutritional supplements for long-term skeletal health and cardiovascular health. To summarise, the following steps may be helpful for building strong bones while maintaining soft and supple arteries: (1) calcium is best obtained from dietary sources rather than supplements; (2) ensure that adequate animal protein intake is coupled with calcium intake of 1000 mg/day; (3) maintain vitamin D levels in the normal range; (4) increase intake of fruits and vegetables to alkalinise the system and promote bone health; (5) concomitantly increase potassium consumption while reducing sodium intake; (6) consider increasing the intake of foods rich in vitamins K1 and K2; (7) consider including bones in the diet; they are a rich source of calcium-hydroxyapatite and many other nutrients needed for building bone.


Key questions

What is already known about this subject?

  • The lifetime risk of osteoporosis is approximately 50%. Most people do not consume the Recommended Daily Allowance of calcium. Traditional mononutrient calcium supplements may not be ideal for promoting long-term cardiovascular and skeletal health.

What does this study add?

  • Calcium is ideally obtained from dietary sources. The form of calcium in bones and bone meal is calcium-hydroxyapatite, which may be particularly effective for building bone.

How might this impact on clinical practice?

  • Increased consumption of calcium-rich foods such as bones, fermented dairy products (e.g. yogurt, kefir, cheese), leafy greens, almonds, and chia seeds may be effective for improving both skeletal and cardiovascular health.


Calcium: general physiology and epidemiology

Calcium is the most ubiquitous mineral in the human body. An average-sized adult body contains approximately 1000 to 1200 g of calcium, which is predominately incorporated into bones and teeth in the form of calcium-hydroxyapatite (Ca10(PO4)6(OH)2) crystals. The remainder circulates throughout the blood and soft tissues, and plays fundamental roles in cell conduction, muscle function, hormone regulation, vitamin (Vit) K-dependent pathways, and cardiac and blood vessel function.1

Some studies indicate only 30% of the US population consumes the Recommended Dietary Allowance of calcium, which is 1000–1200 mg daily.1 Furthermore, humans absorb only about 30% of calcium from foods depending on the specific source.1 The body will demineralise its own skeletal system to maintain serum calcium levels in situations where dietary calcium is insufficient and/or absorption is decreased, and/or excretion is increased.2

Osteopenia/osteoporosis: an epidemic

Starting at about age 50 years, postmenopausal women lose about 0.7–2% of their bone mass each year, while men over age 50 years lose 0.5–0.7% yearly. Between ages 45 and 75 years, women, on average, lose 30% of their bone mass, whereas men lose 15%.

According to the US Surgeon General’s Report, 1 in 2 Americans over age 50 years is expected to have or to be at risk of developing osteoporosis.3 Osteoporosis causes 8.9 million fractures annually, with an estimated cumulative cost of incident fractures predicted at US$474 billion over the next 20 years in the USA.3–6 Among adult women over age 45 years, osteoporosis accounts for more days spent in hospital than many other diseases such as diabetes, myocardial infarction (MI), chronic obstructive airway disease and breast cancer.3 Fragility fractures are the primary cause of hospitalisation and/or death for US adults ≥ age 65 years and older; and 44% of nursing home admissions are due to fractures.3

A Mayo Clinic study reported that compared to 30 years ago, forearm fractures have risen more than 32% in boys and 56% in girls. The authors concluded that dietary changes, including insufficient calcium and excess phosphate, were significantly associated with increased fractures.7 Public health approaches are crucial to prevent symptomatic bone disease, but widespread pharmacological prophylaxis is prohibitively expensive and carries potential serious adverse effects.

Cardiovascular disease and bone mineral disease: a calcium nexus

Strong epidemiological associations exist between decreased bone mineral density (BMD) and increased risk of both cardiovascular (CV) disease and CV death.8 For example, individuals with osteoporosis have a higher risk of coronary artery disease, and vice versa. This problem will be magnified if the therapies for osteoporosis (eg, calcium supplements) independently increase risk of MI.


Maintaining replete magnesium status may reduce risk for the metabolic syndrome, diabetes, hypertension and MI.30 Circumstantial and experimental evidence has also implicated magnesium deficiency in osteoporosis.31–34 Optimal dietary magnesium intake is about 7–10 mg/kg/day, preferably in the context of a net base-yielding diet, since a net acid-yielding diet increases excretion of both magnesium and calcium (table 2).

Table 2

Magnesium dietary sources

Potassium/sodium ratio affects calcium metabolism

A potassium/sodium ratio of 1.0 or higher is associated with a 50% lower risk of CVD and total mortality compared with a ratio under 1.0.35 Reducing excessive sodium intake is also associated with resultant decreased urinary calcium excretion, which may help to prevent against bone demineralisation.36 The average potassium content (about 2600 mg/day) of the typical US diet is substantially lower than its sodium content (about 3300 mg/day).35 Approximately 77% of dietary sodium chloride is consumed in the form of processed foods. By contrast, potassium is naturally abundant in many unprocessed foods, especially vegetables, fruits, tubers, nuts, legumes, fish and seafood. In fact, a high potassium/sodium ratio is a reliable marker for high intake of plant foods and lower intake of processed foods.35 High dietary sodium intake has been associated with endothelial damage, arterial stiffness, decreased nitric oxide production and increased levels of transforming growth factor β; whereas, high potassium dietary intake can counteract these effects.35 36

Evidence indicates that the lowest CV event rates occur in the moderate sodium excretion and high potassium excretion groups.37 Thus, it appears that a moderate sodium diet (2800–3300 mg/day) in conjunction with a high potassium intake (>3000 mg/day) might confer the optimal CV benefits for the general population.37

Vit K and bone health

Emerging evidence suggests that Vit K may confer protective effects for both the skeletal and CV systems. Vit K operates in the context of other fat-soluble vitamins, such as A and D, all of which are involved in maintenance of serum calcium concentration, along with the manipulation of materials leading to bone morphogenesis and maintenance of bone tissue.38 Specifically, the oxidation of Vit K results in activation/carboxylation of matrix Gla protein (MGP) which is partially responsible for mineralising bone.39

Also, Vit K is required for the activation (γ-carboxylation) of osteocalcin; the inactivated form, or per cent of undercaboxylated-osteocalcin (%ucOC), has been found to be a sensitive indicator of Vit K nutrition status.38 In cross-sectional and prospective analyses, elevated %ucOC, which occurs when Vit K status is low, is a marker of increased risk for hip fracture in the elderly.38

Several large observational studies appear to support the benefits of Vit K on bone health.38 A meta-analysis concluded that while supplementation with phytonadione (Vit K1) improved bone health, Vit K2 was even more effective in this regard.40 This large and statistically rigorous meta-analysis concluded that high Vit K2 levels were associated with reduced vertebral fractures by approximately 60% (95% CI 0.25% to 0.65%), hip fractures by 77% (95% CI 0.12% to 0.47%), and all non-vertebral fractures by approximately 81% (95% CI 0.11% to 0.35%). Moreover, the benefit of Vit K on bone may not be due to its ability to increase BMD, but rather to its effects at increasing bone strength.41

Vit K benefits in CV health

Mounting evidence suggests vascular calcification whether in the coronary or peripheral arteries is a powerful predictor of CV morbidity and all-cause mortality.42 Prevention of vascular calcification is therefore important as an early intervention to potentially improve long-term CV prognosis.

A major calcification inhibitory factor, is a Vit K-dependent protein synthesised by vascular smooth muscle cells.42 Increased Vit K2 intake has been associated with decreased arterial calcium deposition and the ability to reverse vascular calcification in animal models. Vit K2 prevents pathological calcification in soft tissues via the carboxylation of protective MGP. The undercarboxylated (inactive) species of MGP is formed during inadequate Vit K status, or as a result of Vit K antagonists.42 Low Vit K status is associated with increased vascular calcifications, and can be improved by effective Vit K supplementation (table 3).4344 In two different randomised, double-blind controlled trials, supplemental Vit K has been shown to significantly delay both the development of coronary artery calcification and the deterioration of arterial elasticity.45 46

Table 3

Vitamin K1 dietary sources

Dietary Vit K exists as two major forms: phylloquinone (K1) and menaquinones (MK-n). K1, the predominant dietary form of Vit K, is abundant in dark-green leafy vegetables and seeds. The main dietary sources for MK-n in Western populations are fermented foods, especially natto, cheese and curds (mainly MK-8 and MK-9).47

Calcium supplementation and bone health

A recent large meta-analysis of 26 randomised controlled trials reported that calcium supplements lowered the risk of any fracture by a modest but statistically significant 11% (n=58 573; RR 0.89, 95% CI 0.81 to 0.96).48

Importantly, a low dietary calcium intake with or without calcium supplementation is also associated with higher CV morbidity and mortality rates.51

Figure 3

Relationship of daily calcium intake to risk of CV mortality during follow-up. Data were fully adjusted for confounding variables. The calcium intake for optimising CV longevity is about 1000 mg/day, with higher and lower calcium intakes associated

Elevated serum calcium concentrations are associated with carotid artery plaque thickness, arterial and aortic calcification, and incidence of MI.57 58 Transient elevations in serum calcium levels have been noted following ingestion of 500–1000 mg of calcium supplements.63 64 By contrast, calcium from dietary sources or bone (calcium hydroxyapatite) ingestion results in much smaller changes in circulating calcium levels.

A plant-rich, grain-free diet alters the acid–base status so as to be slightly alkaline, which is conducive for bone health. However, plants are relatively poor sources of calcium compared to animal sources such as dairy products and animal bones. We suspect that milk, though an excellent source of bioavailable calcium, has potential adverse health effects for some individuals. Additionally, 65% of the world’s population show some decrease in lactase activity during adulthood. Importantly, fermented dairy has been linked to favourable outcomes for bone health and mortality risk.

In a small placebo-controlled randomised trial, women who took 1000 mg of calcium in the form of hydroxyapatite in conjunction with oral Vit D showed a significant increase in bone thickness, whereas those who took 1000 mg of a standard calcium carbonate supplement did not (figure 4).

In theory, consuming calcium-rich foods such as bones, fermented dairy (eg, unsweetened yogurt, kefir, cheese), leafy greens, almonds, and chia seeds may be an effective strategy for improving both calcium intake and long-term health.

Leg cramps, heart muscles, magnesium and CQ10

Minerals for the heart

The heart rhythm is dependant on the movement of minerals across the heart lining.  The heart is trigged to beat by this movement.  Arteries and veins are lined with muscle, which also responds to mineral treatments. Leg cramps can be giving you cues that your body lacks magnesium. And after an intense exercise, your heart muscles need to be nourished with whole foods and CQ10.


Women who supplement only with calcium or people who eat a standard American diet are typically deficient in magnesium.  A standard American diet consists of high sugar, high-refined carbohydrates, low protein, and high fat.

Always supplement calcium with magnesium and use a 1:1 ratio of calcium and magnesium if you tend to have high blood pressure, restless leg syndrome, headaches or muscle cramps.  Otherwise have a 1:2 ratio of magnesium to calcium.  This means with 1500 mg of calcium per day, you should use 750-1500 mg magnesium on the same day.

Magnesium relaxes muscle cells and helps regulate heart rhythm.  It does, however, tend to cause diarrhea, and some forms cause looser stools than others.

Which form of magnesium to use?

Constipation: If you don’t have a complete bowel movement daily use magnesium citrate which helps relax bowel spasms and is an osmotic laxative (see the section on constipation for more information).  Magnesium citrate is a non-addictive and gentle laxative.  To determine the level of magnesium citrate to take, start with 1/day with or without food.  Then daily, increase by 1.  Stop when stools are normal. For instance, 1-2 magnesium citrate 1-2X/day is a common dosage.

Regular bowel movements: If you tend to be regular or have loose stools, use magnesium glycinate or magnesium taurate.

Dosage of magnesium: anywhere from 100-1500mg/day depending on blood pressure.


Taurine is an amino acid normally made in the liver.  Unlike most amino acids, which are hooked together to make proteins, taurine’s function is to shuttle minerals into the heart.  It improves your body’s sensitivity to the minerals you obtain from diet or supplements.

Taurine is especially useful for people who use many medications, or who use medications that damage liver function (e.g. heart medicines including beta blockers and cholesterol medicines.)

It is also useful for those who have adrenal stress, malabsorption, excessive perspiration, or people who have eaten a poor diet all their lives, and currently experience inefficient mineral use.

Taurine dosage: 500-1000mg up to 3 times a day, based on blood pressure, cramping or muscle twitching.



CoQ10 is a molecule necessary for the production of energy in the body.  The body has a series of molecules that shuffle electrons from one to the next (called the electron transport chain).  This shuttle of electrons (electricity) is used to make energy for the body.  The last molecule in this energy transfer is CoQ10.  The molecule made for energy storage is called ATP.  CoQ10 feeds the ATP producing molecule, which causes stores of bodily fuel to be built up.

Muscles require ATP to relax, not contract.  This means muscles contract “for free”, but then need energy to relax again.  This is why deceased people with rigor mortis become “stiff”.  After death, energy production ceases, as does the relaxation of muscles.

CoQ10 supplies energy to the muscles to help them function.

Beta-blockers and some cholesterol lowering medication deplete the body of CoQ10, therefore depleting the body of energy.

Your heart medicines and cholesterol medicines may be harming your heart by depleting its energy!  The very treatment you use to lower your blood pressure or cholesterol can be giving you cramps and robbing your heart of energy.

Vitamin EThree very large studies found 40% heart disease risk reduction with supplements. 

Anti-Alzheimer’s; helps diabetes and dialysis problems and it’s an important anti-inflammatory.

about 200 IU type ‘d’, not ‘dl’. MIXED ‘tocopherols’ best. Relaxes arteries. Always take in oil or fatty meal –AJCN: 1-2004]

Here’s a summary of the excellent 1999 book The Vitamin E factor
Antioxidant; protects blood fats; keeps cholesterol “happy”.  Prevents blood sticking, clots and artery damage.  Like vitamin C, keeps blood and cell fats non-toxic.Very important.  Take during “fattiest” meal.  Natural (d) type doubly effective –also consider: mixed “tocopherols” and possibly “mixed tocotrienols”.  Consider starting with lower dose.  IF on Coumadin (warfarin), aspirin and/or high fish oil, use lowest dose: while preventing clotting, you could promote excessive bleeding.

As with the heart-healthy omega-3 oils, E’s cardio benefits increase with time.  The evidence for prevention is stronger than for E as a cure.

Vitamin Cnot Ester-C238 references in Am J Cl Nutr; June ’99.

Beneficial roles of very high doses in disease are probable but not well established.C, easy to take for granted, hard to underestimate!

1/2 – 4 grams.
At or above lower dose in health, higher in illness.If prone to oxalate type kidney stones, stay below 1 g, drink sufficient water, consider vitamin B6, low salt, low protein and high calcium foods.
Antioxidant.  Works with and recycles vitamin E; Keeps blood vessels healthy; raises ‘good’ & lowers Lp(a) cholesterol; speeds up bowel, reduces length & severity of colds.  Improves general health: point 2 in [31 Comments] and the Linus Pauling Institute.Anti-viral.  At 4 ¢/g, best health bargain around.  99.9% of animals make their own in “mega” amounts as do all plants.  We, monkeys and guinea pigs do not.  Very high dose is remarkably safe: “..take as much as you like” [from the L. Pauling Institute’s Top Ten, May 2000]. Very important.  Nature’s nitroglycerin, like arginine & vitamin E.
The B’s  –No reported toxicity in doses mentioned.(B2), B6, B12 & folic acid will lower artery toxic homocysteine in anyone.Take as a multi and not individually unless there is a special reason.

B1   25-100 mg
B2   25-100 mg
B3 50-600 mg
B6   25-100 mg
B12  100 mcg+B9 = folic acid 800 – 2000 mcg

Pantothenic acid  (B5) 25-200 mg 

They help digest fats and sugars, lower homocysteine (-best in higher than RDA amounts) and reduce plaque.
Very high dose plain B3 niacin (about 0.7g taken after each of meals) is by far the best & cheapest cholesterol “modifying” drug, raising HDL while lowering LDL, Lp(a), fibrinogen and triglycerides –must take with a daily multi.  B3 is also good for your liver and brain.
The B’s are needed for 100’s of processes in the body.  Ultra high doses of some have anti-Alzheimer’s, schizophrenia & depression links. 

The higher doses mentioned resemble Pauling’s.  Very important.  Very high B6 may help carpal tunnel problems.

Calcium (see minerals, below) + Vitamin D, the sun shine vitamin (very important). I’d use calcium combined with magnesium. Calcium 1.2 gr. + Vitamin D 1200 IU (BMJ; Nov. 28 ’98); up to 100 mcg = 4000 IU likely safe AJCN; Dec. ’01) 1.2g Ca + 800IU D prevent bone loss and fracture at age 84! (here’s your reference).  Calcium is heart healthy: bone, boiled egg shell, oyster shell, dolomite, milk (may be) & soy, and green leaf or cabbage type veggie (which also have the bone-building vitamin K).  D = extremely important: fish liver [oil], fatty fish, high-sun on skin; science ref’s: “D”-council & Oregon State.
Magnesium (for more, and for potassium** see minerals, below) 1/2 – 1 gr. Crucial for heart function; it, and potassium** regulate heart beat.  Mg is needed for 325 reactions, not least the lowering of toxic blood homocysteine.  90% of Mg is removed from refined grains and rice!  Most Americans don’t get the RDA of about 0.4 gr. Very important and few side effects.
Selenium (see minerals, below) 200 mcg (max. 800 mcg) Antioxidant, works with vitamins E and C.  A lack causes heart disease, some virus diseases & cancer which are, in part, selenium deficiency diseases. Very important.
CoQ10 (CoenzymeQ10,  or ubiquinone) 60 to 300 mg  Essential for heart & blood pressure; larger dose for serious heart trouble or cancer; vital when taking a “statin” drug.  Body makes less when older (using most B vitamins and magnesium).  Safe but expensive ($1/100mg).  Doubly absorbed when chewed in oily food.
Vitamin F -with the F from Fat …
An old term that shouldn’t be lost.
α-Linolenic; omega-3 (ω-3 or n-3) type oil.

Linoleic; omega-6 (ω-6 or n-6) type oil.

Omega-3: 1 to 2 tea spoons flax/lin or fish, or 2 table spoons canola oil [like: colza, rape, raap, kool, mustard], or soy -only if you can’t find canola.Other types of omega-3 in fatty fish.

Most people get too much n-6.

True vitamins: needed for heart-health. The only 2 fat types (“poly”-unsaturates) the body can not make itself.Omega-3 type alpha-linolenic is scarce in the Western food supply but key to heart, general and mental health.  Fish oil works like a-linolenic, see: [Good Food] and point 1 in [31 Comments] and lowers triglycerides.

Omega-6 type linoleic (corn, sun, saff, soy, cotton) is rarely lacking and is often excessive in relation to n-3 linolenic.  Probably the most common “vitamin overdose” in Western diets at 2x-3x the ISSFAL maximum for most people.  The cancer-link keeps on popping up in the high omega-6 research.


*Minerals are complicated as there are many and it is possible to overdose.  Intakes depend on the degree of food processing and amounts in the soil.  Plants make vitamins but must mine their minerals -if not in the soil, it won’t be in the plant.  Here’s some info about their roles –not necessarily as supplements- in health and disease.
Selenium: vital: US Nat. Inst. of Health

200 mcg before and in HIV / AIDS & virus infections (book or free 700k pdf): low selenium lowers resistance -including to viruses that steal your selenium- making things seriously worse.Low selenium makes every infection worse since it’s needed in your T lymphocyte defense system.

NE, SE and NW N-Am. & North Europe, New Zealand, parts of China: under 50 mcg/day & often insufficient.Southern Europe and a central N-S band in N-Am. seem to have adequate amounts in the soil.  Large local differences (also: point 14 in Comments). 200-800mcg.

The higher dose is above what is generally accepted as safe but may well slash the US cancer death rate by about one quarter [my guess] as well as the spread of AIDS [someone else’s guess].

Zero reported deaths from supplements. Toxicity likely at 2500 mcg/d.

Cancer, heart disease, heart muscle, muscle, cataracts, blood pressure, some virus diseases, aging
Overdose risk -as per the top link in the left column- should be weighed against potentially 6 fewer cancer deaths per 100 N. Americans on high dose selenium.
Some whole grains, fish, Brazil nuts, kidney and, more reliably, supplements:Twinlab’s Daily One Cap, a Best Buy, almost uniquely contains an excellent 200 mcg, see [Nuts, Bolts] for all sources.


20 – 50 mg (not well absorbed) 5 – 10 mg or higher Bones, joints, heart, skin, poor (weak) collagen Unrefined plants and greens, whole grain, horsetail plant. Dietary fiber (oats, barley, and rice) and wine. 


30 mcg (US) often insufficient 200-400 mcg 
with selenium
Diabetes; helps insulin, cholesterol, acne, sugar use Liver, grains, root veggies, green pepper.
Vanadium 10 – 60 mg often insufficient 100 mcg+ Diabetes; higher doses replace insulin Shell fish, parsley, some processed foods, grains, beans.
Boron 1.5 mg often insufficient 3 – 9 mg Bone health, diabetes, infection, arthritis Water, fruits, veggies.
Manganese 2.5 – 4 mg often insufficient 5-15 mg Bone, cartilage, heart, epilepsy, diabetes, cataracts  Unrefined vegetarian; not in animal products. 

The ONLY nutrient deficiency known to raise LDL cholesterol.

Without it artery structure is not made, or repaired!

0.7 -1.5 mg often insufficient  1-2 mg (1/10th of your zinc intake) Like selenium & iron, don’t overdose on copper Heart, arthritis, hair color, artery bursts (aneurysm, stroke), bad collagen, high LDL, poor clotting, Parkinson’s Nuts, grains, bracelets, supplements.

Soft or acidic water: excessive amounts from copper pipes.
Zinc -Part of 300 enzymes, the nutritional screw drivers, hammers and pliers of our body (protein and fancy oils being the nuts, bolts and batteries, and glucose or fats the fuel). 7-14 mg Low intake is linked to 1.4% of the world’s deaths! [WHO]Rules 2000 cell functions in addition to those 300 enzymes! 10 – 30 mg Arthritis, skin, infection, bad collagen, vision, prostate, diabetes, etc.  Much more from BMJ; 2002-11-9. Shell fish, nuts, grains, beans, potatoes, fish and meat.
Molybdenum 75-250 mcg or less ? 75-250 mcg Organs, enzymes, cancer Whole grains, beans, liver.
U.S. (AIM; 2000-9-11):
young adults: 3.4 g/d; high fruit + veggies: 8 – 11 g/d; urban whites: 2.4 g/d; often elderly or Blacks: ~1 g/d.   20% of hospitalized patients have low potassium.
varies; often insufficient –in relation to sodium i.e. kitchen salt; lost in processing. 2 – 5.6 gr (US RDA)**Try to get it from your food 
Heart, heart failure, stroke, hypertension, cell function, sweating, diuretics, irregular heart beat**, muscle, fatigue, nerves, etc. etc. Bananas, celery, fruits (prune, orange) and veggies (potato, broccoli, beets), meat, fish, salt substitutes.Zero in: white flour, sugar & fats. 
Sodium (salt) most often high or excessive 1/10th of potassium Cell function, always sufficient; raises blood pressure Salted foods; source of vital iodine -check your area.


16 mg (Sweden) often insufficient 10 – 15 mg 
don’t overdose
Blood; premeno- pausal women only; some infants, teens & elderly Liver, nuts, grains & greens; vitamin C increases absorption
Magnesium 300 mg (Sweden)
often insufficient; very important
500 – 1000 mg (at least half of calcium intake) Heart, heart failure, irregular heart beat, bone, PMS, cramps, fatigue, diabetes, stroke, diuretic use, etc. Whole grains, nuts, soy, greens, root veggies & supplements


500 mg (Belgium)
often insufficient
1000 – 2000 mg (1-2g) Bone, heart, general, blood pressure Bone, greens, grains, nuts & milk. Not in meats. 

Mineral needs are complicated because each person’s situation is unique while you or your health-advisor will never know which minerals were in the soil where your food was grown, how much was taken up, or by how much milling and cooking reduced their amount.
Each nutrient is important and wise supplementation with some minerals is a practical way to insure that you get the optimum amounts. 
**POTASSIUMIt now appears quite possible that a lack of potassium in the coronary muscles may be the major cause of death from heart disease in humans ” [Adelle Davis, ’72].  95% of potassium is inside cells, as opposed to sodium, and magnesium keeps it there.  Because raw plant-based diets are high in potassium & low in sodium, well functioning kidneys remove potassium faster than sodium.  Disposal of vegetable cook-water, high salt or low magnesium diets, sweating and most diuretics can cause fatal depletions of potassium and/or magnesium.  References: 1.) irregular heart beat: JAMA; ’99-6-16; 2.) blood pressure: JAMA; ’97-5-28; 3.) stroke: NEJM;’87-1-29 [60% of risk at 4.3 vs. 2.4g/d]; 4.) review BMJ; ’01-9-1 [10 mmole = ~0.4 g].


Does eating a lot of bone extract home prepared soups increase the cholesterol level?

chole-3No. Bone soup is rich in magnesium and when garlic, onions and other greens are added, it is also rich in sulfur, cleansing to the body.

Cholesterol is needed in making hormones.

The cell membranes are weak and lacking in nutrients, hence we have high cholesterol.

Enzymes and Cofactors for life and longevity

General information

Cofactors, mostly metal ions or coenzymes, are inorganic and organic chemicals that assist enzymes during the catalysis of reactions. Coenzymes are non-protein organic molecules that are mostly derivatives of vitamins soluble in water by phosphorylation; they bind apoenzyme to proteins to produce an active holoenzyme. Apoenzymes are enzymes that lack their necessary cofactor(s) for proper functioning; the binding of the enzyme to a coenzyme forms a holoenzyme. Holoenzymes are the active form of an apoenzyme.



Cofactors can be metals or coenzymes, and their primary function is to assist in enzyme activity. They are able to assist in performing certain, necessary, reactions the enzyme cannot perform alone. They are divided into coenzymes and prosthetic groups. A holoenzyme refers to a catalytically active enzyme that consists of both apoenzyme (enzyme without its cofactor(s)) and cofactor. There are two groups of cofactors: metals and small organic molecules called coenzymes. Coenzymes are small organic molecules usually obtained from vitamins. Prosthetic groups refer to tightly bound coenzymes, while cosubstratesrefer to loosely bound coenzymes that are released in the same way as substrates and products. Loosely bound coenzymes differ from substrates in that the same coenzymes may be used by different enzymes in order to bring about proper enzyme activity.

Enzymes without their necessary cofactors are called apoenzymes, which are the inactive form of an enzyme. Cofactors with an apoenzyme are called a holoenzyme, which is the active form.
General formula


Metal cofactors

Metal ions are known as the common cofactors. In some enzymes, the function as a catalyst cannot be carried out if a metal ion is not available to be bound the active site. In daily nutrition, this kind of cofactor plays a role as the essential trace elements such as: iron (Fe3+), manganese (Mn2+), cobalt (Co2+), copper (Cu2+), zinc (Zn2+), selenium (Se2+), and molybdenum (Mo5+). For example, Mg2 is used in glycolysis. In the first step of converting glucose to glucose 6-phosphate, before ATP is used to give ADP and one phosphate group, ATP is bonded to Mg2 which stabilizing the other two phosphate groups so it is easier to release only one phosphate group without resonate with other two. In some bacteria such as genus Azotobacter and Pyrococcus furiosus, metal cofactors are also discovered to play an important role. An example of cofactors in action is the zinc-mediated function of carbonic anhydrase or the magnesium-mediated function of restriction endonuclease.


A coenzyme is a small, organic, non-protein molecules that carries chemical groups between enzymes. It is the cofactor for the enzyme and does not form a permanent part in the enzyme’s structure. Sometimes, they are called cosubstrates and are considered substrates that are loosely bound to the enzyme. In metabolism, coenzymes play a role in group-transfer reactions, such as ATP and coenzyme A, and oxidation-reduction reactions, such as NAD+ and coenzyme Q10. Coenzymes are frequently consumed and recycled. Chemical groups are added and detached continuously by an enzyme. ATP synthase enzyme phosphorylates and converts the ADP to ATP, while Kinase dephosphorylates the ATP back to ADP at continuous rates as well. Coenzyme molecules are mostly derived from vitamins. They are also commonly made from nucleotides such as adenosine triphosphate and coenzyme A.

Through further research in coenzyme activity and its binding effect on the enzyme, more can be revealed about how the enzyme changes conformationally and functionally. An example is of the MAPEG group of integral membrane enzymes. These enzymes are crucial in the catalytic transformation of lipophilic substrates, which are involved in arachidonic acid derived messengers production and xenobiotic detoxification. Through use of a bound detergent to mimic a MAPEG enzyme’s cofactor, glutathione, a new active site specific for lipophilic substrate is revealed; thus, further studies can reveal how these substrates bind to this second form of the enzyme [1].

Vitamin C is an important coenzyme

Vitamin A

Important Coenzymes



nicotinamide adenine dinucleotide is a coenzyme derived from vitamin B3. NAD+ is capable of carrying and transferring electrons and functions as oxidizing agent in redox reactions. It also works as a substrate for DNA ligases in posttranslational modification, where the reaction removes acetyl groups from proteins. Furthermore, in glycolysis and the citric acid cycle, NAD+ oxidizes glucose and releases energy, which is then transferred to NAD+ by reduction to NADH. NADH later on unloads the extra electron through oxidative phosphorylation to generate ATP, which is the energy source humans use every day. In addition to catabolic reactions, NADH is also involved in anabolic reactions such as gluconeogenesis, and it also aids in the production of neurotransmitters in the brain.



flavin adenine dinucleotide is a prosthetic group that, like NADH, functions as a reducing agent in cellular respiration and donates electrons to the electron transport chain.


compounds that have fully conjugated aromatic rings to which two oxygen atoms are bounded as carbonyl groups (i.e. diketones). Quinone’s structure gives them the ability to form substances with colors. They exist as pigments in bacteria, fungi, and certain plants, and give them their characteristic colors. In addition, they are used to manufacture different color dyes for industrial purposes. In biological systems, they serve as electron acceptors (oxidizing agents) in electron transport chains such as those in photosynthesis and aerobic respiration. Many natural or synthetic quinines show biological or pharmacological activities, and some event show antitumoral activities.



coenzyme A, synthesized from pantothenic acid ATP, functions as acyl group carriers to transport functional groups such as acetyl (acetyl-CoA) or thioesters in metabolic reactions like fatty acid oxidation (synthesis of fatty acids) and citric acid cycle (cellular respiration). It also transfers fatty acids from cytoplasm to mitochondria. In addition to its transporter role in metabolism, CoA is also an important molecule in itself. For instance, CoA is an important precursor to HMG-CoA, an important enzyme in the metabolic synthesis of cholesterol and ketones. Furthermore, it contributes the acetyl group to the structure of acetylcholine, which is an important neurotransmitter responsible for inducing muscle contraction.

Common Coenzymes

Vitamin A

Vitamin A is subdivided into two molecules, Vitamin A1 (retinol) and Vitamin A2 (dehydroretinol). Retinol is the most active and common form. Vitamin A has a large conjugated chain which serves as the reactive site of the molecule. Unlike most cofactors, Vitamin A undergoes a sequence of chemical changes (oxidations, reductions, and isomerizations) before returning to its original form. The ability for Vitamin A’s electrons to travel from &pi to &pi* orbital makes it a good candidate molecule for trapping light energy. Consequently, Vitamin A is responsible for transferring light energy to a chemical nerve impulse in the eyeball. Vitamin A is also used for growing healthy new cells such as skin, bones, and hair. It maintains the lining of the urinary tract, intestinal tract, and respiratory system. Additionally, Vitamin A is required for the reproductive functions such as the growth and development of sperm and ovaries.

Vitamin C

Also known as absorbic acid, Vitamin C is quite abundant in most plants and animals excluding primates, guinea pigs, bats, and some birds. Despite human’s inability to synthesis absorbic acid, it is an essential in many biosynthetic pathways such as synthesizing collagen. Deficiency leads to a disease called Scurvy. Vitamin C helps regulate the immune system and relieve pain caused by tired muscles. It also is needed in the manufacture of collagen and norepinephrine. Vitamin C is also an antioxidant which can enhance the immune system by stimulating white blood cells in the body. Vitamin C also helps to benefit the skin, teeth, and bones.

Vitamin B1

Also named Thiamine or Thiamine diphosphate (TPP), Vitamin B1 is a cofactor for oxidative decarboxylation both in the Kreb’s Cycle and in converting pyruvate to acetyl-CoA (an important molecule used in the citric acid cycle of metabolism). It is widely available in the human diet and particularly potent in wheat germ and yeast. It’s functionality results from a thiazole ring which stabilizes charge and electron transfer through resonance.

Vitamin B2

Vitamin B2 is known as riboflavin. Vitamin B2 is the precursor of Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) which are coenzymes used to oxidized substrates. FAD contains riboflavin and adenine. FMN contains riboflavin that is why it is called mononucleotide.

Vitamin B3

Vitamin B3 is Niacin or nicotinic acid with the formula C5H4NCO2H. Vitamin B3 is a precursor to NADH, NAD+, NADP+ and NADPH which are coenzymes found in all living cells. NAD+ and NADP+ are oxidizing agents. NADH and NADPH are reducing agents.

Vitamin B6[edit]

Vitamin B6 is precursor to coenzyme pyridoxal phosphate (PLP) which is required in certain transformation of amino acids including transamination, deamination, and decarboxylation.

Vitamin B12

Vitamin B12 is the name for a class of related compounds that have this vitamin activity. These compounds contain the rare element cobalt. Humans can not synthesis B12 and must obtain it from diet. Enzymes that catalyze certain rearrangement reaction required B12 or its derivatives.

Vitamin H

Also named Biotin, Vitamin H is a carboxyl carrier; it binds CO2 and carries it until the CO2 is donated in carboxylase reactions. It is water soluble and important in the metabolism of fatty acids and the amino acid Leucine. Deficiency leads to dermatitis and hair loss, thus making it a popular ingredient in cosmetics.

Vitamin K

Vitamin K is needed for the process of clotting of blood and Ca2+ binding. Vitamin K can be synthesized by bacteria in the intestines. Vitamin K is needed for catalyzing the carboxylation of the γ-carbon of the glutamate side chain in proteins.

Non-enzymatic cofactors

Cofactor is also used widely in the biological field to refer to molecules that either activate, inhibit or are required for the protein to function. For example, ligands such as hormones that bind to and activate receptor proteins are termed cofactors or coactivators, while molecules that inhibit receptor proteins are termed corepressors.

The coactivator can enhance transcription initiation by stabilizing the formation of the RNA polymerase holoenzyme enabling faster clearance of the promoter.

The corepressor can repress transcriptional initiation by recruiting histone deacetylases which catalyze the removal of acetyl groups from lysine residues. This increases the positive charge on histones which strengthens in the interaction between the histones and DNA, making the latter less accessible to transcription.

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


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.


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.