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Anti-Nutrients and Pro-Nutrients

Deficient vitamin and mineral intakes are common. In the adult population of the United States at least 50% are deficient in Vit A, Vit C, calcium and magnesium, while over 90% are deficient in Vit D and Vitamin E. (ref). And these data don't consider effects of natural anti-nutrients which decrease nutrient bioavailability and add to the shortfall. For those intolerant to many foods and forced to limit their diets, anti-nutrients in those few foods are an even greater concern. Eating a wide range of foods dilutes out the effects of specific antinutrients in a few foods. (e.g. oatmeal at breakfast will not lead to zinc deficiency but oatmeal 3 times a day will, unless supplemented with zinc (as well as copper to keep balance with the extra zinc.) Anti-nutrients are also a concern for those on exclusively plant-based diets, which contain large amounts of antinutrients such as phytates and oxalates that interfere with uptake of divalent minerals such as calcium, copper, zinc and magnesium. Plants also sequester nutrients behind cellulose walls that must be breached by processing methods such as chopping, cutting, thorough chewing and/or cooking.

Nutrient data on food packaging or websites such as SelfNutritionData, which has data from the USDA's National Nutrient Database, is only a starting point in determining diet quality.

The best overall source of information on vitamins, minerals, other nutrients, and nutrient interactions is the Linus Pauling Institute Micronutrient Information Center website (connected to Oregon State University)

Anti-Vitamins and Pro-Vitamins
  1 – Water-Soluble Vitamins,
  2 – Fat-Soluble Vitamins
Balancing Act–Notes


Water Soluble Vitamins:

B1 – THIAMINE (Coenzyme functions in metabolism of carbohydrates and branched chain amino acids; deficiency results in overall decrease in carbohydrate metabolism and its interconnection with amino acid metabolism (via a–keto acids) results in decrease in the formation of acetylcholine for neural function. Diets high in carbs require higher intake of thiamin than diets high in fat. (p. 70 of ref) Deficiency causes beriberi, polyneuritis, and Wernicke-Korsakoff syndrome) Deficiency stems from inadequate dietary intake from: 1) foods initially low in thiamine or exposed to prolonged high temperatures, 2) increased requirement (alcoholism, severe infections – eg. malaria AIDS, 3) excessive loss (diuretic use, hemodialysis), 4) folate and magnesium status, "Adequate folate status is considered essential for carrier-mediated thiamin absorption because folate is required for production of transport proteins and maintenance of intestinal integrity" ref, ref. Magnesium deficiency may need to be corrected before complete remission of symptoms of thiamine deficiency ref and/or 5) consumption of foods rich in Anti-Thiamine Factors (ATFs), of which there are 2 types:

    •  RAW MUSSELS, SOME VARIETIES OF CRABS, and raw organs of fresh-water fish such as carp (but not in muscle tissue) contain Anti-Thiamine Factors that are thermolabile (can be heat inactivated).
    •  CERTAIN POLYPHENOLS IN TEA AND COFFEE, ESPECIALLY EXTRACTS such as SVETOL from green coffee beans. These contain Anti-Thiamine Factors that are heat-stable such as caffeic acid and chlorogenic acids (ortho-dihydroxy and para-hydroxy polyphenols; rich sources include tea and coffee, but may not be significant esp. if consumed apart from meals. [In a population of Irish women that routinely drink large quantities of tea and coffee, poor thiamine status was not dependent on polyphenol intake but on inadequate thiamine dietary intake.  Influence of folate status and polyphenol intake on thiamine status of Irish women (1990). Svetol, a standardized green coffee extract of chlorogenic acid, is used as a food additive in coffee products, chewing gum, and mints. ref. [Currently, in many countries, thiamine enrichment of processed grain products such as flour, pasta and rice is routine; without enrichment marginal or deficient thiamine status would be much more common].
    •  HIGH PROLONGED COOKING TEMPERATURE inactivates thiamine in food.
To best absorb dietary thiamine, avoid high prolonged cooking temperatures, and only consume tea and coffee between meals.

B2 – RIBOFLAVIN (Coenzyme functions in numerous oxidation and reduction reactions; symptoms of deficiency – reduction in growth, cheilosis, angular stomatitis, and dermatitis). Alcoholics are at increased risk of riboflavin deficiency. Clinical deficiency is rare in the developed world but suboptimal serum riboflavin appears to be common, even though dietary intake may be adequate. Erythrocyte Glutathione Reductase Activation Coefficient (EGRAC) a measure of riboflavin status showed a majority of population in England tested deficient but without functional abnormalities (ref. p. 70)
     • THE ACKEE PLUM in Jamaica causes "vomiting sickness" and is the only known natural riboflavin antagonist.

B3 – NIACIN, NICOTINAMIDE (Co substrate/coenzyme for hydrogen transfer with numerous dehydrogenases; deficiency is called pellagra, a chronic wasting disease associated with dermatitis, dementia preceded by mental changes including insomnia and apathy, and diarrhea from inflammation of the intestine; Conversion of tryptophan to niacin equivalents via the kynurenin pathway requires riboflavin (vit B-2), vitamin B-6, and iron; deficiencies of these nutrients as well as other disturbances in tryptophan metabolism may also contribute to pellagra. [Niacin and nicotinamide undergo catabolism via SAMe-dependent methylase enzymes. Large doses of supplemental niacin or nicotinamide may lead to SAMe deficiency with many side effects due to the over 100 SAMe-dependent methylase reactions. Recently large doses of niacin have been found not to reduce risk of heart disease even though it raises HDL.]
     • BOUND NIACIN: Cereal grains such as corn, oats, wheat and grain sorghum contain bound Vitamin B3 (probably bound to glycoproteins) that makes it unavailable unless released by alkaline/lime treatment, such as done during processing of masa corn meal and corn tortillas.

Nutritional data on niacin content in grains does not take into account that bound niacin can't be absorbed.

B5 – PANTOTHENIC ACID (Constituent of coenzyme A and phosphopantetheine involved in fatty acid metabolism; deficiency symptoms – Fatigue, sleep disturbances, impaired coordination, and nausea). There don't seem to be many, if any, natural anti-pantothenic acid substances that effect humans. Deficiency only occurs in severely malnourished people or those treated with a lab-created antagonist, omega-methylpantothenic acid. "A metabolic antagonist of pantothenic acid, PANTOYL G-AMINO BUTRYIC ACID (called pantoyl-GABA, homopantothenate, or hopantothenate), is widely used in Japan as an anti-dementia drug for treating cognitive impairments in pathological states such as Alzheimer's disease, presumably through increasing cholinergic activity in vivo. Reyes-like syndrome has been reported in patients using pantoyl-GABA, presumably due to pantothenic acid deficiency." ref.
     • BIOTIN?? Pantothenate has a similar structure to biotin and both share the same carrier protein. If biotin is supplemented at high enough levels, that might interfere with pantothenate uptake. See biotin below:

Take biotin supplements separate from pantothenic acid supplements, and vice versa. Does not apply to multivitamins that contain only small amounts of both (less than or equal to 100% RDA or 100% Daily Value)

BIOTIN – Coenzyme functions in bicarbonate–dependent carboxylations; Symptoms of deficiency include growth retardation, fatigue, depression, nausea, dermatitis, and muscular pains.
    • HIGH DOSES OF VITAMIN B5 (PANTOTHENIC ACID), but not low doses, inhibit uptake of biotin because both share the same multivitamin transporter in the small intestine. Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. Said et al (1998). "...the concentration of pantothenic acid in most foods and biological fluids is approximately 200 times the concentration of biotin; theoretically, pantothenic acid might substantially reduce biotin transport via competition. ...[But] Pantothenic acid at 10 to 1,000 nmol/L reduced biotin (475 pmol/L) uptake by less than 12% (P < 0.05). [Human peripheral blood mononuclear cells: Inhibition of biotin transport by reversible competition with pantothenic acid is quantitatively minor. Zempleni and Mock (1999)].

(For those in the majority with normal biotinidase enzyme, slight inhibition of biotin uptake would likely not matter, but for those with low function biotinidase, this inhibition of biotin uptake might be serious.)

    •  RAW EGG WHITE contains avidin, which in the intestinal tract forms a stable complex with biotin and renders it inactive.
     • ALPHA-LIPOIC ACID may compete with biotin for transport across cell membranes because both share, along with pantothenic acid (vitamin B5), the same transporter protein. (ref. Lipoic Acid Reduces the Activities of Biotin-Dependent Carboxylases in Rat Liver)

– As above with pantothenic acid, take biotin supplements separately from pantothenic (-ate) acid supplements, and especially do not take mega doses of pantothenic acid, particularly for the 4% of population with heterozygous low activity biotinidase enzyme.
– Consider that large amounts of alpha-lipoic acid (ALA) may interfere with biotin uptake. –note: supplemental biotin may interfere with the most commonly used thyrotropin and thyroid hormone assays and mimics the typical laboratory pattern for Graves’ disease. ref

B6 – PYRIDOXINE, PYRIDOXAL-5'-PHOSPHATE (Coenzyme in over 100 enzymes including all transamination reactions, and in certain decarboxylation, deamination, and racemization reactions of amino acids, and includes synthesis of serotonin, an important precursor to melatonin—which is necessary to initiate and maintain sleep. Symptoms of deficiency – Nasolateral seborrhoea, glossitis, and peripheral neuropathy). Inflammation in the body is associated with lower B6 levels. See Linus Pauling Institute B6 article, and "Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of US adults" Sakakeeny et al.(2012) Whether active B6 supplements will help lower inflammation is not known. But pyridoxine (not P-5-P) supplements do not seem to improve inflammation in rheumatoid arthritis patients– ref.
    • FLAXSEED Meal (but not the oil) contains a natural anti-B6 called linatine. Linatine hydrolyzes to glutamic acid and 1-amino-d-proline, which forms a stable complex with pyridoxal-5'-phosphate, inactivating it as a vitamin. Chicks eating flaxseed meal develop B6 deficiency and need pyridoxine supplementation; but flaxseed has not been reported to be associated with B6 deficiency in humans ref.
(However, I experienced onset of severe insomnia while taking one teaspoon ground flaxseed at 2 out of 3 meals daily. I would lie awake all night long, which was scary for someone, who'd never had trouble sleeping. An internet search turned up information on anti-B6 linatine in flaxseed, which made me realize that inhibition of melatonin synthesis via an upstream B6 dependent reaction might be involved. I added supplemental pyridoxal-5-phosphate (not at same time as flax) and made sure to eat ground flaxseed at only one meal. Voila, sleep again was easy!!! My problem with flaxseed was probably worsened by having two variant high activity alleles of the ALPL gene, which codes for an enzyme that metabolizes and lowers Vit B6 blood levels. See risk alleles for B6 serum levels given by 23andMe.)  See also Sleep Quality in the Survival of Elderly Taiwanese: Roles for Dietary Diversity and Pyridoxine in Men and Women, by Huang et al (2014)  Women who slept poorly had lower vegetable and vitamin B-6 intakes compared to good sleepers. For men, good and fair sleepers had a lower risk of death compared to poor sleepers. For both men and women, greater dietary diversity scores and fair to good sleep and adequate plasma pyridoxal phosphate (PLP), reduced risk of death. For women serum PLP predicted mortality better than quality of sleep.)
   •  PYRIDOXINE B6 Pyridoxine at high enough levels does not convert fast enough to the active form, pyridoxal-5-phosphate; and the unchanged pyridoxine blocks active B6 from binding to B6-dependent enzymes. See "The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function" Vrolijk et al. (2017) "The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency." Thus the reports of toxic neuropathy from high levels of pyridoxine. Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy A prospective study of pyridoxine neurotoxicity. Berger et al (1992)

– Flaxseed has great nutritional value, but limit to one meal per day. Take multivitamin or supplemental B6 at a meal other than the flaxseed-containing one. Prefer the active form of B6 found in the body, pyridoxal-5-phosphate, because pyridoxine at high enough levels inhibits B6-dependent enzymes and causes the same symptoms as B6 deficiency.

VITAMIN B-12 (cyanocobalamine, methy-cobalamine, hydroxy-cobalamine, adeno-cobalamine)
     • ACID REDUCING MEDICATION such as Proton Pump Inhibitors (e.g. Prilosec and Aciphex), and Histamine 2 Receptor Antagonists (e.g. Pepsid, Zantac) increase risk of Vit B12 deficiency. See Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency Results: "...Both a 2 or more years’ supply of PPIs (OR, 1.65 [95% CI, 1.58-1.73]) and a 2 or more years’ supply of H2RAs (OR, 1.25 [95%CI, 1.17-1.34]) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95%CI, 1.77-2.15]) than were doses less than 0.75 pills/d (OR, 1.63 [95%CI, 1.48-1.78]; P = .007 for interaction).
     • VITAMIN C?: A report claiming destruction of B12 by megadoses of Vitamin C is most likely non-significant – "The interaction between vitamin B12 and vitamin C" – a refutation by Hogenkamp.
     • FOLATE: "increasing folate status due to folic acid fortification and/or folic acid supplementation has been demonstrated to accelerate and worsen both the metabolic and the clinical consequences of B12 deficiency" ref "The Transcobalamin II (TCN2) 776C/G polymorphism is associated with increased odds of peripheral neuropathy in the elderly, even with normal vitamin B-12 status, especially if their folate intake is >2 times the Recommended Dietary Allowance.[>800mcg/day]" ref
How much folate to lower serum homocysteine if heat labile MTHFR variant is present (rs1801133(C>T)/C677T)? After folic acid supplementation to 400 micrograms, TT homozygotes still had slightly higher homocysteine levels than CC subjects but not by much, 9.5 vs 8.1 µmol/L. On the low folate exclusion diet TT homozygotes had 14.5 µmol/L homocysteine vs. CC homozygotes at 8.9 µmol/L. ref

If possible avoid acid–lowering medications, which increase risk of B12 deficiency. Do not supplement with more than 800 micrograms of folic acid or other forms of folate to avoid increased risk of B12 deficiency–caused neuropathy. Those with low activity MTHFR variants may need only 400 micrograms supplementary folate to adequately bring down homocysteine levels. ref

FOLATE (Folic acid, folate, folinic acid)
     • GREEN TEA AND EXTRACTS Effects of folate cycle disruption by the green tea polyphenol epigallocatechin-3-gallate Navarro-Peran et al (2007) "...tea polyphenol, epigallocatechin-3-gallate, is an efficient inhibitor of human dihydrofolate reductase. Like other antifolate compounds, epigallocatechin-3-gallate acts by disturbing folic acid metabolism in cells, causing the inhibition of DNA and RNA synthesis and altering DNA methylation. Epigallocatechin-3-gallate was seen to inhibit the growth of a human colon carcinoma cell line in a concentration and time dependent manner....epigallocatechin-3-gallate causes adenosine to be released from the cells because it disrupts the purine metabolism. [However, in our human pilot study, no differences in plasma folate concentrations in response to dietary GTC (Green Tea Catechins) supplementation were observed, see review article on Flavonoids]
" Association between the serum folate levels and tea consumption during pregnancy Shiraishi et al (2012) "high consumption of green tea or oolong tea ... associated with a low serum folate level during pregnancy, after adjusting for confounding variables including dietary folate intake and use of folic acid supplements or multivitamins (β = −0.131, p = 0.016).

VITAMIN C (ascorbic acid, ascorbate)
     • COOKING: Vitamin C is the most thermolabile vitamin (for roots and tubers: 20 - 30 % loss from boiling and baking, 10 - 21 % loss from leaching into cooking water. Roasting and frying may be worse. Loss is less for unpeeled vegetables.)
     • STORAGE: Up to 40 - 60% loss of Vit C content in potato depending on length of storage.
     • FLAVONOIDS such as quercetin inhibit sodium dependent vit C transporter 1 in cultured cells and in rats, but has not been investigated in humans. See Review article Which Sources of Flavonoids: Complex Diets or Dietary Supplements?

Take multi–vitamins with food that contains enough fat/oil to insure bioavailability of fat-soluble vitamins in the multi– as well as fat-soluble vitamins in the food itself.

VITAMIN A AND PROVITAMIN A CAROTENOIDS (15 carotenoids) note: The relative bioavailability of β-carotene from vegetables compared with purified β-carotene ranges between 3 to 6% from green leafy vegetables, 19 to 34% for carrots and 22 to 24% for broccoli. ref. Dietary Factors That Affect the Bioavailability of Carotenoids
     • VERY LOW FAT MEALS: Carotene-rich plant foods need dietary fat for absorption; only 2.4 gram fat /meal yielded similar rise in serum provitamin A carotenoid concentrations compared to 10 gram fat per meal. Carotene-rich plant foods ingested with minimal dietary fat enhance the total-body vitamin A pool size in Filipino schoolchildren as assessed by stable-isotope-dilution methodology. B-carotene absorbed better with long chain triglycerides vs. medium chain triglycerides, which are absorbed mainly through portal vein, resulting in low chylomicron formation. B-carotene needs to be incorporated into chylomicrons for absorption into lymphatic system.
     • LUTEIN may inhibit absorption of B-carotene. ref
     • VITAMIN E in small amounts stabilizes Vit A and carotenoids, which because of their unsaturated bonds are easily destroyed by oxidizing agents. But in large amounts vitamin E inhibits absorption.

NON-PROVITAMIN A CAROTENOIDS–INCLUDING LUTEIN AND ZEAXANTHIN (note: relative bioavailability of lutein (67%) from a diet that includes a variety of vegetables is much greater than for β-carotene (14%) Dietary Factors That Affect the Bioavailability of Carotenoids
     • HIGH FAT MEAL: plasma lutein response was higher (207% increase) when lutein esters were consumed with 36 grams fat than with 3 grams (88% increase). Amount of fat in the diet affects bioavailability of lutein esters but not of α-carotene, β-carotene, and vitamin E in humans
     • B-CAROTENE may reduce absorption of lutein and canthaxanthin. ref

– Co-ingest at least 3 grams of fat/oil with vegetables to absorb beta-carotene.
– Co-ingest lutein and zeaxanthin-rich vegetables with several grams of fat/oil, and do not consume supplemental beta carotene at the same meal.
– Cooking and thorough chewing increases absorption of carotenoids.
– Carotenoid-rich foods gives the skin a golden glow, but some people have genetic variants (see BCMO1 gene) that make them prone to turning yellow or orange with carotenoid supplements.

     • VERY LOW FAT MEALS: Vit D is fat–soluble and requires dietary fat for uptake, but low fat cheese fortified with 28,000 IU Vit D3 once a week resulted in the same rise in serum 25(OH)D level as Vit D-fortified regular fat cheese. The Bioavailability of Vitamin D from Fortified Cheeses and Supplements Is Equivalent in Adults, Wagner et al, 2008.
     • EXCESSIVE HIGH DOSE VITAMIN D SUPPLEMENTATION: Bolus high-dose vitamin D3 supplementation (70,000 IU once per week) appeared to increase breakdown of Vit D even after stopping the high dose, and causing a decline in blood levels of Vit D–25[OH] and its active metabolite–1,25[OH]2D. The 35,000 IU per week did not result in significant increase of Vit D breakdown. Lower doses of vitamin D3 ingested frequently may be the best method, and to stop Vit D supplementation do it gradually. [Ref.]
     • GREEN PLANTS: A number of incompletely characterized natural substances in green plants that may include beta-carotene or other compounds with a steroid structure, reduced by 50% the activity of a curative dose of Vit D3 in hens. (in Toxicants Occurring Naturally in Foods, National Academy of Sciences, 2nd edition 1973)
     • POLYUNSATURATED FATTY ACIDS and SATURATED FATTY ACIDS (bad or good?): PUFAs and SFAs have been reported to reduce effectiveness of Vit D3 supplementation in healthy older adults, and MONOUNSATURATED FATTY ACIDS may improve it. See Type of Dietary Fat Is Associated with the 25-Hydroxyvitamin D3 Increment in Response to Vitamin D Supplementation (Niramitmahapanya, Harris and Dawson-Hughes , 2011) A major limitation of this study was use of food frequency questionnaires to estimate intakes of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and saturated fatty acids (SFA).
   A recent study in older people, using actual plasma 25-hydroxyvitamin D measurements, reported that a meal with 30% calories as fat significantly enhanced absorption of 50,000 IU of Vit D3 compared to a fat-free meal, and presence of high PUFA and low MUFA did not affect this outcome. Dietary Fat Increases Vitamin D-3 Absorption (Dawson-Hughes et al, 2014) Limitations: Hugh amount of Vit D was being used rather than lower doses over time.
     • MAGNESIUM increases Vit D serum levels, since it is essential for synthesis and metabolism of vitamin D. High intake of magnesium was associated with reduced risks of Vit D deficiency and insufficiency. (see Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III.) Also see: Role of Magnesium in Vitamin D Activation and Function, Uwitonze and Rassaque (2018) and "Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial" by Dai Q et al (Am J Clin Nutri 2018)
     • CALCIUM – "High dietary calcium intake has a vitamin D–sparing effect, because it increases the half-life of 25(OH)D." but suppresses conversion of 25(0H)D to active form, 1,25-dihydroxyvitamin D.  Diet, sun, and lifestyle as determinants of vitamin D status. Lips et al (2014)  (Calcium supplements inhibit magnesium absorption so try to avoid taking both at the same meal.)

     • OPTIMAL VIT D LEVELS: A study in Denmark found that in diabetics, both high and low serum Vit D levels (less than 20 ng/ml or greater than 50 ng/ml, optimal 20 - 50 ng/ml) were associated with cardiovascular autonomic neuropathy, which may cause low blood pressure on standing and exercise intolerance. May explain association of higher vit D levels with falls and increased mortality.ref
  High dose Vit D may decrease natural production of melatonin.The influence of vitamin D supplementation on melatonin status in patients with multiple sclerosis. Golan et al. (2013) Twenty one MS patients took 800 IU of vitamin D3 per day (low dose), while 19 patients received 4,370 IU vitamin D3 per day (high dose) for one year. After 3 months supplementation, 25-OH-D levels increased and nighttime melatonin secretion decreased significantly in the high dose group, but not in the low dose group. After 1 year, a decrease in 25-OH-D levels associated with increase in patient BMI, was accompanied by an increase of urine nighttime 6-SMT in the high dose group. Along the same lines: Repletion of vitamin D associated with deterioration of sleep quality among postmenopausal women. Mason et al. (2016) Postmenopausal women whose serum Vit D rose above 32 ng/ml in response to supplementing 2000 IU vit D3 per day during a weight loss and exercise program had worse sleep quality than women whose serum Vit D stayed below 32 ng/m despite supplementation or did not have supplementation.
   High dose Vit D may increase risk and duration of upper respiratory infections/colds, but not acute respiratory infections. (I had 3 colds in 3 months on 4500 IU/day Vitamin D3 when I usually had none. A reduced dose of 2500 IU/day, resulted in no colds for over 2 years now.) Double-blind randomized controlled trial of vitamin D3 supplementation for the prevention of acute respiratory infection in older adults and their carers (ViDiFlu) Martineau et al. (2015)

– to optimize absorption of Vit D supplements, co-ingest with several grams of fat/oil (monounsaturated?).
– if taken with a meal, perhaps avoid co-ingestion with carotenoid-rich vegetables.
– Make sure to get sufficient magnesium to help increase serum levels of Vit D. (Magnesium oxide is poorly absorbed, and most magnesium in grains and nuts is not bioavailable.) Supplementing with a more soluble compound such as magnesium citrate improves Vitamin D levels and also improves symptoms of magnesium deficiency such as leg muscle spasms at night.
– There may be negative side effects above optimal Vit D supplementation (serum levels greater than 50 ng/ml).

VITAMIN E (see Vitamins C and E: Beneficial effects from a mechanistic perspective)
     • CO-INGESTON WITH A MEAL- HIGH FAT VS LOW FAT?: Vit E absorption improves with a meal. (Bioavailability of Vitamin E as Function of Food Intake in Healthy Subjects, Iuliano et al, 2001). In one report there was significantly greater plasma-labeled alpha-tocopherol concentrations when the capsule was consumed with a high-fat meal (17.5 g) versus a low-fat meal (2.7 g), and there was also a difference between a high-fat toast and butter and a cereal with full-fat milk meal (both 17.5 g fat), indicating that both the amount of fat and food matrix is important for vitamin E absorption. (Physiological factors influencing vitamin E biokinetics. Lodge et al, 2004). Another study reported that a hot meal with 3 gram of fat increased plasma Vit E by 20% but a meal with high-fat spread containing 36 grams of fat increased serum Vit E by 23% - not much more than the low-fat spread. ( see Amount of fat in the diet affects bioavailability of lutein esters but not of α-carotene, β-carotene, and vitamin E in humans, Roodenburg et al, 2000).
     • BEANS Unclear reports of antivitamin E factors in beans (kidney beans). One heat stable and ether soluble (linoleic acid? Possibly from increased need for Vit E activity in unsaturated fatty acids.) and one heat labile (cooking destroys) and insoluble in ether (organic solvent). (In Toxicants occurring naturally in foods, National Academy of Sciences 2nd edition -1973)  
    • UNSATURATED FATTY ACIDS Vit E requirements increase with amount and degree of unsaturation of fatty acids above the minimum basal requirement of 4 - 5 mg/d of RRR-α-tocopherol (most supplemental Vit E is a 50:50 mix of L and R a-tocopherol so divide that in half to get the amount of R form only):

FA name Oleic Linoleic a-Linolenic Arachidonic EPA DHA
Structure 18:1 18:2 18:3 20:4 20:5 22:6
# of double bonds 1 2 3 4 5 6
Mg vitE/g FA 0.075 0.5 (.4-.6) 0.75 1.0 1.25 1.5

Formula for Vit E requirements: 4.5 (basal req.) + 0.075 x grams DB1 + 0.5 x grams DB2 + 0.75 x grams DB3 + 1.0 x grams DB4 + 1.25 x grams DB4 + 1.5 x grams DB5 = milligrams natural RRR-α-tocopherol. (formula reference)

Vitamin E function and requirements in relation to PUFA – Raederstorff et al.

It can be difficult to get sufficient Vit E from daily food intake but natural sources are preferred to supplements because varying amounts of the 7 other forms of Vit E are also present. Check Vit E (alpha tocopherol) amount in daily diet at SelfNutritionData. If insufficient, perhaps supplement with natural D-alpha with mixed tocopherols vs. synthetic DL alpha tocopherol. But try to stay with smaller doses because Vit E interferes with the function of Vit K in blood clotting and perhaps bone metabolism. Also high amounts of supplemental antioxidants such as Vit E and Vit C may interfere with beneficial cellular response to resistance exercise. (see ref) and for ultramarathoners, supplementation for 2 months with 800 mg. Vit E as D-alpha-tocopherol showed pro-oxidant and pro-inflammatory effects, contrary to expectations  (ref). (To limit dose of Vit E, perhaps take an E capsule every two or three days or poke a hole in a 200 IU capsule, and squeeze out a couple drops into food once a day and use the same capsule over a few days. But that can get messy.)

VITAMIN K (Vitamin K: the effect on health beyond coagulation – an overview) and The role of vitamin K in soft-tissue calcification.
     • LOW FAT MEALS: If spinach is eaten without fat, the amount of K1 that is absorbed is reduced 70%. Gijsbers et al conclude that bioavailability of vegetable K1 is very poor unless taken with fat, and that supplemental Vit K is more bioavailable (Effect of food composition on vitamin K absorption in human volunteers). K2 bioavailability is small at 8.8 grams of fat and much higher at 35 grams fat per meal. Effect of dietary fat content on oral bioavailability of menatetrenone in humans.
     • LARGE DOSES OF VITAMIN E (1000 IU alpha tocopherol/day for 12 weeks) interfered significantly with Vit K activity involved in blood clotting (3 - 10 fold increase in under-gammma-carboxylation of prothrombin) and may contribute to excessive bleeding. ref "Individuals taking anticoagulatory drugs like warfarin and those who are vitamin K deficient should not take vitamin E supplements without close medical supervision because of the increased risk of hemorrhage." ref. The mechanism is unknown (ref). The K vitamins are required for gamma carboxylation of several bone-related proteins including osteocalcin, a bone matrix protein, and Gla-protein, which inhibits vascular calcification (ref). Low vitamin K intake is associated with increased risk of osteoporotic fracture. (ref)

To more efficiently absorb Vit K co-ingest with fat/oil and chew vegetables thoroughly. Do not take large doses of supplemental Vit E, which interfere with Vit K activity.


      • CALCIUM – With increasing amounts of calcium in a meal, fractional calcium absorption (%) decreases. Half a gram (500 mg) of calcium either as calcium carbonate (consumed with a meal) or as calcium citrate (alone or with a meal) is the optimum dose, though of the two, calcium citrate is the better absorbed ref (Difference in absorption, probably explains my severe constipation on calcium citrate while calcium carbonate is not a problem.)
     • VITAMIN D: "Absorptive efficiency increases as serum 25-hydroxyvitamin D [25(OH)D] rises, up to ≈80 nmol/L [32 ng/ml]; above this level, additional increases in vitamin D status have no further effect on absorptive regulation.... Vitamin D mediates active calcium absorption, without active transport a much higher intake of calcium is needed - 1100 mg/d just to avoid net loss of calcium; 3000 mg/d to net 200 mg/d the minimum needed to offset obligatory losses." (Vitamin D and calcium interactions: functional outcomes, Heaney, 2008)
    • OXALATE — Calcium absorption is inversely proportional to oxalic acid content of the food (The higher the oxalic acid, the lower the availability of calcium). Calcium bioavailability is low for the high amounts of oxalate in foods such as spinach, rhubarb, nuts, some grains etc. Spinach is high in calcium, but actually a poor source because the calcium is bound to calcium oxalate – 100 grams of raw baby spinach has about 1000** milligrams (mg) of total oxalate of which 768 mg. is soluble and easily absorbed into the body, while the rest is in insoluble form, mostly as calcium oxalate, which is not absorbed. Food that contains high levels of soluble oxalate extract calcium and other mineral cations from foods or supplements that are consumed at the same meal ref (250 mg oxalate [C 2 O4] binds about 78 mg calcium [Ca++] to form 328 mgs insoluble calcium oxalate [CaC2O4] – This is my calculation based on one mole of calcium binding with one mole of oxalate to form one mole of calcium oxalate) **The most up-to-date list of food oxalate levels can be found by joining the Yahoo Group – Trying Low Oxalates at https://groups.yahoo.com/neo/groups/Trying_Low_Oxalates/info. Luckily most foods do not have as much oxalate as spinach, rhubarb or almonds.
References for oxalates: Effect of dietary calcium on urinary oxalate excretion after oxalate loads (Liebman and Chai, 1997) "...dietary calcium can reduce oxalate absorption and excretion. " Calcium carbonate and calcium citrate malate were equally effective. A minimum of 200 mg elemental Ca lower absorption of 198 mg oxalic acid the best. Mean 24-h oxalate absorption was 5.9% with 200 mg Ca and 7.6% with 300 mg Ca. Absorption was 9.1% with 100 mg Ca and 11.3% with oxalic acid alone. Maximum reduction in oxalate absorption occurred at a molar ratio of 2.0 - 2.5 Calcium to 1 of oxalic acid.
Note: presence of high phytate, which binds calcium, increases absorption of oxalate.
     • PHYTATE – Calcium bioavailability is less impacted by high levels of phytate than other minerals such as zinc and copper.
     • SODIUM CHLORIDE (table salt) – 26 mg of calcium per day is lost in the urine of women and 39 mg of men (ref.) for each 1 gram of sodium excreted in urine, and most of dietary sodium is excreted. The basal sodium requirement for both young and adult humans is no greater than 8 to 10mmol/day (equivalent to about 500 mg of salt). ref. See also Adverse Effects of Sodium Chloride on Bone in the Aging Human Population Resulting from Habitual Consumption of Typical American Diets (Frassetto et al. 2008) "...diets that contain substantial sodium chloride and diets that are net acid producing each independently induce and sustain increased acidity of body fluid. With increasing age, the kidney's ability to excrete daily net acid loads declines, invoking homeostatically increased utilization of base stores (bone, skeletal muscle) on a daily basis to mitigate the otherwise increasing baseline metabolic acidosis, which results in increased calciuria and net losses of body calcium. Potassium Citrate Prevents Increased Urine Calcium Excretion and Bone Resorption Induced by a High Sodium Chloride Diet (Sellmeyer et al., 2002) The addition of oral potassium citrate to a high-salt diet prevented increased excretion of urine calcium and bone resorption markers caused by a high salt intake.
     • PROTEIN (BAD or GOOD?) – More protein in the diet results in greater calcium excretion. But where does the extra urinary calcium come from? Is it from our bones, or from increased absorption of dietary calcium? One study used isotope labeled calcium and showed that higher urinary calcium levels from the high protein diet (2.1 gram protein/kg. body weight) was due to a greater calcium absorption of 26% versus 19% absorption from the moderate protein diet (1.0 gram protein/kg. body weight) and resultant excretion of the labeled calcium. Furthermore, the high protein diet caused a significant reduction in the fraction of urinary calcium coming from bone. In the short-term high protein diet did not harm bone health. See The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. (Kerstetter et al., 2005) Calcium loss in urine may also be related to need for buffering the acid load after consuming high amounts of sulfur-containing amino acids such as methionine, cysteine and cystine (which are high in animal protein, and cereal proteins such as in oatmeal). But dietary acid load may not matter except in older men. see Dietary Acid Load Is Not Associated with Lower Bone Mineral Density Except in Older Men (McLean et al., 2011)
Low protein intakes are tied to low calcium absorption. Low Protein Intake: The Impact on Calcium and Bone Homeostasis in Humans. also see Protein intake, calcium balance and health consequences (Calvez et al. 2012) "...HP [High Protein] intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. ...in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet." Also A Diet High in Meat Protein and Potential Renal Acid Load Increases Fractional Calcium Absorption and Urinary Calcium Excretion without Affecting Markers of Bone Resorption or Formation in Postmenopausal Women (Cao et al, 2011). See also Dietary protein and bone health: a systematic review and meta-analysis ( Darling et al, 2009) "...first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. ....A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine Bone Mineral Density."
Conclusion: A diet high in animal and grain proteins does not appear to increase and may help to decrease risk of low bone density. However, since more calcium is excreted in high protein diets, the risk of calcium oxalate kidney stones may be increased.
     • STOMACH ACID LOWERING MEDICATIONS SUCH AS PPIs, reduce absorption of calcium carbonate supplements, but for Calcium Citrate. Taking calcium carbonate with food increases absorption even in presence of low acid stomach. Calcium in milk and other dairy products is absorbed well in low acid stomach. (An Evaluation of the Importance of Gastric Acid Secretion in the Absorption of Dietary Calcium. Bo-Linn et al,.1983; Gastric acidity, atrophic gastritis, and calcium absorption. Wood and Lacrosniere, 1992).
     • CAFFEINE– On average, a cup (240 mL) of coffee decreases calcium retention by only 2–3 mg. ref
     • PHOSPHORUS consumption reduces calcium loss in urine, by increasing renal tubular reabsorption of calcium. ref Milk has optimum phosphate levels for calcium absorption.

– For better calcium retention, lower dietary sodium to recommended levels (< 2300 mg/day for most, but 1,500 mg/day for certain other groups - CDC).
– If a condition of low stomach acid is present, take insoluble calcium supplements with meals. (not necessary for calcium citrate or milk)
– Take calcium with sufficient bioavailable phosphorus (phosphorus in grains is strongly bound into phytates and not bioavailable), recommended levels of dietary protein and Vit D.
– Calcium inhibits uptake of several minerals. Take calcium separately from Zinc and Magnesium supplements.
I generally have 2 small snacks/day of a beverage (such as milk) spiked with calcium carbonate (to make about 400 mg total Ca each snack) apart from main meals. These snacks usually consist of small amounts of the high oxalate foods in my diet such as nuts. Some of the calcium will bind soluble oxalate (the kind that is absorbed) and limit uptake of the oxalate and also a small amount of the calcium. High levels of dietary oxalate increase risk of calcium-oxalate kidney stones, especially in those at risk.
Precaution: More than 1.5 grams of calcium per day (especially calcium carbonate, which is alkaline) along with ingested alkali (aluminum and magnesium hydroxide) predisposes to a dangerous condition called calcium-alkali (a.k.a. milk-alkali) syndrome. May cause calcium deposits in tissues, kidney failure and kidney stones. More information.

COPPER (deficiency causes anemia unresponsive to iron therapy, but corrected by copper supplementation; and neutropenia (low numbers of white bloods cells called neutrophils). Heart tissue has a strong requirement due to high oxidative stress ameliorated by copper/zinc-superoxide dismutase. Copper deficiency may also cause loss of pigmentation, neurological symptoms, impaired growth (ref), and lowers ability to metabolize histamine in the gut by impairing DAO histaminase activity. However, a high level of copper in the blood – particularly non-ceruloplasmin copper from water in contact with copper plumbing and multivitamins – may contribute to Alzheimer's risk, ref and Links between copper and cholesterol in Alzheimer's disease (Hung et al. 2013) and Disturbed Copper Bioavailability in Alzheimer's Disease (Kaden et al. 2011). Copper has a specific transporter Biochemical characterization and subcellular localization of human copper transporter 1 (hCTR1)
     • HIGH VIT C (ascorbic acid) is antagonistic to copper absorption. Influence of ascorbic acid supplementation on copper status in young adult men by Finley and Cerklewski (1983) "Subjects consuming self-selected diets took 500 mg of ascorbic acid with each meal (1500 mg/day) for 64 days."
     • TANNINS in tea or outer "skin" of nuts bind copper and inhibit absorption.
     • ZINC "When zinc and copper ranges were varied within a relatively normal range, there was no inhibitory effect on copper absorption."(Bioavailability of Copper, Bo Lonnerdal, 1996) But High Zinc supplementation increases synthesis of intestinal metallothionein, which binds certain metals and prevents absorption in order to regulate intake – a way to avoid metal toxicity. Metallothionein has greater affinity for copper than zinc, so high levels of metallothionein caused by high dietary zinc decreases copper absorption."If dietary zinc is increased from 5 to 20 mg/d (76 to 306 m mol/day), the intake of copper needs to be 60% higher to maintain balance. Further indication of the delicate interaction between the two elements came from a study by Greger and Snedeker (Copper absorption and bioavailability, Wapnir, 1998) that showed that only 3 mg/day more of zinc sufficed to increase copper losses and diminish copper retention."Symptoms of zinc toxicity are mainly due to copper deficiency. High copper intakes do not appear to affect zinc serum levels. (I developed signs of copper deficiency, with 18 mg of zinc supplementation. My reaction was insomnia, probably due to arousal effects of high brain histamine from hyper-reactive mast cells (mast cell activation disease) and reduced ability to metabolize histamine due to low activity copper-dependant DAO histaminase enzyme [homozygous low activity alleles in the AOC1 (a.k.a. ABP1) gene, which encodes for DAO enzyme -23andMe data.])
     • MAGNESIUM & SELENIUM – "Copper absorption as affected by supplemental calcium, magnesium, manganese, selenium and potassium" (1989, Kies and Harms). "Results indicated that the calcium supplements depressed fecal copper losses and improved body copper retention as did potassium supplements. Magnesium and selenium supplementation of diets resulted in increased apparent fecal losses of copper while no effect of manganese supplementation was found." ref - Copper bioavailability and requirements (1982) [Copper] Requirement is highest when dietary zinc is high and protein is low, and lowest when dietary protein is high and zinc is low.
     • CALCIUM & POTASSIUM "...calcium supplements depressed fecal copper losses and improved body copper retention as did potassium supplements." (ref)
     • PHYTATE, Copper is second only to zinc in the formation of stable complexes with phytate. In descending order of stability: zinc>copper>nickel>cobalt>manganese>calcium>iron Absorption of less stable complexes and absorption is not inhibited as much. However, consuming lots of high phytate grains seems to inhibit zinc absorption more than copper absorption. May be because phytate containing foods (plant-based) have more copper to begin with so lower absorption is made up by higher amount. See next...
     • ANIMAL PROTEIN VS. PLANT-PROTEIN DIET, "Copper absorption was higher from the animal-protein diet (41 %) than from the plant-protein diet (34%) in nonpregnant women. However, the copper content of the plant-protein diet was higher, resulting in more copper being absorbed from it than from the animal-protein diet." (ref)

– For better copper absorption avoid high zinc and Vit C supplementation (amount considered high depends on the individual) .
– Limit high tannin–containing foods such as raw nuts with skins, and tea to one meal per day or between meals.
– Magnesium and selenium supplements may inhibit uptake of copper so limit to one meal per day or between meals.

Long term inorganic copper supplements are not recommended due to possible connection with Alzheimer's. Currently, all copper supplements are inorganic even if they say chelated or amino acid chelated etc. True organic copper is incorporated as a cofactor into certain enzymes, mainly oxidases, made by living organisms and need to be consumed from an animal or plant.

     CRUCIFEROUS/BRASSICA AND SOME NON-BRASSICA VEGETABLES – brassica: kale, collard greens, cabbage, Brussels sprouts, kohlrabi, broccoli, cauliflower, bok choy, rapini (broccoli rabe), chinese cabbage, napa cabbage, turnip root, rutabaga, canola/rapeseed, mustard seeds, mustard greens, black arugula (rocket), garden cress, watercress, radish, daikon, wasabi; non-brassica: includes carrots, sweet potato and beans [non-brassica contain less cyanogenic glucosides, less than half the glucosinolates and about the same amount of thiocyanates as brassica - ref]. These veggies contain many different kinds of glucosinolates, the products of which may decrease risk of various cancers but at same time specific ones have mutagenic, cytotoxic, and thyroid damaging properties. Glucosinolates are hydrolyzed by the plant's innate myrosinase enzyme, which is released by damage to the plant such as cutting or chewing. Breakdown products of glucosinolates include isothiocyanates, nitriles, and thiocyanates. It's the thiocyanates that are reported to stimulate detoxification enzymes and reduce cancer risk. Some isothiocyanates interfere with thyroid hormone synthesis by thyroid (goitrogens). Other breakdown products, such as thiocyanates compete with iodine absorption by the thyroid, but toxicity can be overcome by additional iodine. Effects of these compounds:
     — Thiocyanate ions interfere with iodine uptake by the thyroid. However, preexisting iodine deficiency is usually needed for ordinary amounts of dietary cruciferous vegetables to cause hypothyroidism unless large amounts of raw (such as juiced) cruciferous vegetables are eaten. (see Effect of processing on glucosinolate content, below**)
     — Nitriles
     • 5-vinyloxazolidine-2-thione and similar goitrogens are a more serious problem since they interfere with actual thyroid hormone synthesis and the effects are not overcome by increase in dietary iodine.
     • Thioureas, another type of goitrogen formed from isothiocyanates.

**Effect of processing on glucosinolate content:
— An 88-year-old woman developing severe hypothyroidism and coma following consumption of 1.0 to 1.5 kg or 2.2 to 3.3 pounds/day of raw bok choy for several months. Myxedema Coma Induced by Ingestion of Raw Bok Choy (2010)).
— One study in humans found that consumption of 150 g/day (5 oz/day) of cooked Brussels sprouts for four weeks had no adverse effects on thyroid function. Preliminary observations on the effect of dietary brussels sprouts on thyroid function by McMillan et al (1986) reported that in spite of brussels sprouts high content of glucosinolates that form goitrogen 5-vinyloxazolidine-2-thione, there was no effect on thyrotrophic hormone, thyroxine and tri-iodothyronine. "It is suggested that this lack of activity of cooked Brussels sprouts is due to inactivation during cooking of myrosinase, the specific glucosinolate-degrading enzyme.
— Kinetic study of the irreversible thermal and pressure inactivation of myrosinase from broccoli (Brassica oleracea L. Cv. italica) Ludikhuyze et al (1999). "Thermal inactivation (of myrosinase from broccoli) proceeded in the temperature range 30-60 degrees C [86–140° F]." But there is not complete lack of myrosinase activity because intestinal bacteria produce myrosinase that allows for some formation and absorption of isothiocyanates, but much lower absorption than from cooked. Newer studies show that broccoli myrosinase is not completely inactivated by steaming to 70 degrees C until crisp, tender. What is inactivated is a co-enzyme that produces an alternate product that does not have the cancer-fighting properties of sulforaphane. Most of the enzyme that produces sulforaphane is intact. See this video by Rhonda Patrick for benefits of sulforaphane and the best methods to obtain it.
— Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Shapiro et al (1998) Cooking for 30 minutes significantly reduces the amount of goitrogens.
— Effect of storage, processing and cooking on glucosinolate content of Brassica vegetables. [in broccoli, Brussels sprouts, cauliflower and green cabbage] From the Abstract: "... Bioavailability of glucosinolates and related isothiocyanates are influenced by storage and culinary processing of Brassica vegetables. ... Storage at ambient temperature and in a domestic refrigerator showed no significant difference and a minor loss (9-26%) of glucosinolate levels over 7 days. Vegetables shredded finely showed a marked decline of glucosinolate level with post-shredding dwell time - up to 75% over 6h. Glucosinolate losses were detected partly as isothiocyanates. Cooking by steaming, microwaving and stir-fry did not produce significant loss of glucosinolates whereas boiling showed significant losses by leaching into cooking water. Most of the loss of the glucosinolates (approximately 90%) was detected in the cooking water. "

 — Flavonoids and Isoflavones may exhibit antithyroid and goitrogenic activity. Ferreira et al. (Inhibition of thyroid type 1 deiodinase activity by flavonoids.) studied the in vitro effects of various flavonoids on thyroid type 1 iodothyronine deiodinase activity in a murine thyroid microsome fraction and found type 1 iodothyronine deiodinase activity significantly inhibited by isoflavones, quercetin, and catechins. For more information see the review: Which Sources of Flavonoids: Complex Diets or Dietary Supplements?

Cook Brassica vegetables to reduce potential goitrin and thiocyanate levels by 2/3rds. If pre-existing issue with low/hypo thyroid, then boil Brassica vegetables to leach out goitrins and thiocyanates into cooking water. Make sure to get daily recommended amount of iodine.

IRON – INORGANIC NONHEME AND ORGANIC HEME — Iron deficiency is a cause of anemia, symptoms include fatigue, shortness of breath, and muscle weakness. Iron overload is also a risk factor in several illnesses including neurodegeneration, cirrhosis of the liver, of illness including symptoms of neurotoxicity, liver damage, too much increases risk of cardiovascular disease, liver disease, Alzheimer's and diabetes— seek the middle to low middle road. (ref) Dietary Iron Intake and Body Iron Stores Are Associated with Risk of Coronary Heart Disease in a Meta-Analysis of Prospective Cohort Studies Hunnicutt et al (2014)
     • CALCIUM and milk products inhibit both nonheme and heme iron absorption
     • PHYTATE "iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. "(ref.)
     • POLYPHENOLS "The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing more than 100 mg tannic acid." (ref) "Quercetin Inhibits Intestinal Iron Absorption and Ferroportin Transporter Expression In Vivo and In Vitro" Lesjak et al (2014)
     • LONG TERM PPI USE may increase risk of iron deficiency. (Proton Pump Inhibitors and Risk of Vitamin and Mineral Deficiency, Heidelbaugh, 2013)
     • CHRONIC INFLAMATION and DEPRESSION: The body uses an evolutionary strategy to lower available iron during signs of a bacterial infection, thus lowering growth rates of bacteria. The signs that may be elicited by a bacterial infection include lack of energy or depressed state, higher levels of inflammatory mediators, higher body temperature/fever etc. even if there isn't an actual infection, but a chronic illness such as autoimmune disease. Thus in depression or chronic inflammation, anemia can result. See "Anemia of Inflammation" Nemeth and Ganz (2014). And Found My Fitness podcast with Dr. Charles Raison. Dr. Charles Raison on Depression, the Immune-Brain Interface & Whole-Body Hyperthermia
     • VITAMIN C enhances uptake of inorganic iron
     • MEAT enhances iron uptake. Meat also provides heme-iron which is more easily absorbed than inorganic iron supplement. (Calcium and dairy products can also interfere with heme-iron uptake, but the problem is not as severe as with inorganic iron supplements.)
     • Alcohol Consumption

For more efficient absorption of nonheme iron, avoid the following at the same meal: high calcium-containing products such as dairy and calcium supplements, tannin-containing foods such as skins of nuts and tea, and high phytate containing foods such as many grains and nuts. Co-ingestion of vitamin C supplement helps overcome inhibition of inorganic iron uptake by tannins and phytates in the same meal. Organic heme-iron from animal products is more efficiently absorbed, though high calcium will still inhibit uptake. Post menopausal women and men do not need as much iron as younger women; pregnant women and growing children need more. Too much iron is toxic (hemochromatosis), but iron deficiency anemia is common, and causes symptoms such as fatigue, pale skin, shortness of breath etc. Suspected anemia should be tested for, and appropriate supplements or diet change implemented if needed. Low iron stores alone (ferritin levels < 50 ug/L) without frank anemia may be a cause of chronic fatigue. See the article: "Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial" Vaucher et al. (2012).

MAGNESIUM (see review Dietary Factors Influencing Magnesium Absorption in Humans (Bohn, 2008) "... low Mg serum levels have been associated with a number of chronic diseases including diabetes mellitus type II, cardiovascular disease, osteoporosis and the metabolic syndrome." Frank magnesium deficiency with neuromuscular symptoms such as cramping are rare. [But a supplement of magnesium citrate, not magnesium oxide, helped my night-time leg cramps.] Also see this recent review, Magnesium in Prevention and Therapy by Frober et al (2015)

     • With increasing amounts of magnesium in a meal, fractional magnesium absorption (%) decreases.
     • Supplemental Magnesium Oxide has poor solubility and is associated with low Mg bioavailability in humans when compared to Mg citrate, and other compounds or chelates of magnesium.
     • PHYTATE The following order of stability between phytic acid and trace elements [Cu>Zn>Mn>Mg>Co>Ni] ref (other refs have Zn first and Cu next and yet Zn absorption is affected much more than copper absorption). Magnesium uptake not affected as much as Zinc in presence of high phytate levels.
     • OXALATE – Magnesium oxalate is more soluble that calcium oxalate so the bioavailability of magnesium is greater in presence of soluble oxalates than for calcium (though not much of calcium is actually needed to bind average amounts of oxalate.) But magnesium supplements still help prevent oxalate absorption.
     • LONG TERM PPI USE is associated with risk of magnesium deficiency. (Proton Pump Inhibitors and Risk of Vitamin and Mineral Deficiency
     • CALCIUM – "...addition of calcium to the diet in amounts ranging from 300 to 1000 mg/d decreased Mg absorption significantly in healthy subjects at Mg concentrations typically ingested with the diet (370 mg/d). But "The majority of studies in humans did not indicate an effect of consuming up to 2000 mg calcium/d on Mg absorption." ????
     • ZINC – very high doses of supplemental zinc (142 mg, which is 13 times the required intake of 11 mg daily for adult men) interfere with absorption of magnesium. Inhibitory effects of zinc on magnesium balance and magnesium absorption in man. Spencer et al, 1994.
For more efficient absorption of magnesium consider not taking supplemental calcium at the same meal. Bioavailability of magnesium in grains and nuts is low. Consider a magnesium supplement other than mag oxide and containing less than 100% RDA. Excess magnesium supplementation may have severe effects; tolerable upper intake level for adults is 350 mg supplemental magnesium. 170 mg magnesium citrate/day fixed my night-time leg cramps.

SELENIUM ((In those with selenium deficiency, addition selenium may decrease the risk of cancer (ref). A study of African-American women in the U.S. found that those supplementing with greater than or equal to 20 mcg/day had about 30% lower risk of ovarian cancer.)
(Effects of dietary copper, cadmium, iron, molybdenum and manganese on selenium utilization by the rat. 1986) "...it is unlikely that copper, cadmium, iron, molybdenum and manganese at normal dietary concentrations will have a major effect on selenium metabolism in the rat, especially if adequate amounts of selenium are being consumed."

ZINC (see Overview of Zinc Absorption and Excretion in the Human Gastrointestinal Tract, Zinc: Nutrient Reference Values for Australia and New Zealand and FAO Document, Chapter 16. Zinc [In a high fiber vegetarian diet, of all the minerals, low bioavailability of Zinc is the most problematic. ref]
     • ZINC – With increasing amounts of zinc in a meal, fractional zinc absorption (%) decreases.
     • PHYTATE – a fiber composed of phosphorylated forms of inositol phosphate that is found in corn, cereals, rice, legumes. Phosphate groups of phytate form strong, insoluble complexes with mineral cations (such as zinc); the gastrointestinal tract of humans and other mammals does not contain phytase to break down phytate and release the minerals. (What this means is that the mineral content claimed for unfortified, unmodified high phytate whole grains, does not take into account low bioavailability. Much of the iron, magnesium, manganese, selenium, calcium, zinc is not bioavailable!) See tables of phytate values
     • CALCIUM?? - Co-ingestion of calcium supplements, such as calcium carbonate and calcium citrate, may (ref) or may not result in less absorption of zinc supplements. – Dietary Factors Influencing Zinc Absorption by Lonnerdal (2000) ; but may depend on presence of phytate to form insoluble complexes ref. However this study using radio-labeled zinc and defined diets by Hunt and Beiseigel, 2009 found that "Differences in dietary calcium did not affect zinc absorption in women, regardless of a high or low dietary phytate content."
     • IRON (as inorganic iron such as ferrous gluconate) supplements (38-65 mg/day) may impair zinc absorption (but does not affect copper absorption, though copper, iron, and zinc share divalent metal transporter 1(DMT-1) and under certain conditions competitively inhibit each other. But inconsistent findings in literature. (ref) Another study reports that "Simultaneous addition of zinc [zinc oxide] and iron [reduced elemental iron] to corn tortilla does not modify zinc bioavailability at iron doses of 30 and 60 mg/kg of corn flour. It appears that if food is fortified with reasonable amounts of iron there is no adverse effect on zinc absorption. (ref)
     • LOW STOMACH ACID inhibits zinc uptake from zinc oxide, which has low solubility unless normal gastric acidity and consumed during a meal. Water–soluble zinc compounds (zinc sulfate gluconate, acetate etc.) are better absorbed in low acid stomachs. (ref)
     • ANIMAL PROTEIN - The amount of animal protein in a meal is positively correlated with zinc absorption and can counteract the inhibitory effect of phytate, but casein in milk has a negative effect. ref

To more efficiently absorb zinc, avoid iron supplements and probably avoid calcium supplements and high calcium dairy at the same meal. Consuming lots of phytate-containing grains such as oatmeal at every meal definitely requires a zinc supplement. (see a doctor for blood zinc test) But it's a balancing act between zinc and copper. Taking too much zinc causes copper deficiency. Taking too little zinc causes zinc deficiency, but copper levels are higher. Human stores of zinc and copper exist in dynamic equilibrium; an increase in one causes a fall in the other, and may produce clinical consequences of toxicity or deficiency in one or the other.

ANTI-PROTEINS but these are usually accounted for in **PDCAAS (Protein Digestibility-Corrected Amino Acid Score)
      • Tannins: Found in high amounts in tea, skins of nuts, green bananas, unripe persimmons and other unripe fruit, chocolate, coffee, darker colored beans, barley, beer and wine.
         "...the presence of high levels of tannins in cereals, such as sorghum, and grain legumes, such as fava bean (Vicia faba L.), can result in significantly reduced protein and amino acid digestibilities (up to 23%) in rats, poultry, and pigs."
        And can trigger IBS symptoms and cause constipation or make is much worse. "Tannin acid reduced small intestinal secretions and inhibits peristalsis.... Eating unripe bananas can cause green banana constipation. Green bananas contain 100-250 mg tannins/100 g and have high amylase-resistant starch content. Constipation inducing property of bananas has been used in the BRAT (banana, rice, apple sauce, and toast) diet for diarrhea. Reference: "Diets for Constipation" by Sun Hwan Bae (2014) On the other hand, green kiwi fruit improves GI motility: "Clinical studies in a range of adult populations consistently indicate that kiwifruit are a highly effective dietary option to promote laxation. This, together with emerging evidence for the putative effects of kiwifruit in beneficially promoting gastric emptying and digesta mixing, suggests that kiwifruit are physiologically active throughout the gastrointestinal tract." in the abstract: "Kiwifruit modulation of gastrointestinal motility" (2013) and article: "Putative mechanisms of kiwifruit on maintenance of normal gastrointestinal function" by Bayer, Drummond and Gearry 2017.
      •Enzyme Inhibitors: "The presence of high levels of dietary trypsin inhibitors from soybeans, kidney beans, or other grain legumes can cause substantial reductions in protein and amino acid digestibilities (up to 50%) in rats and pigs."
      • Phytates: "Studies involving phytase supplementation of production rations for swine or poultry have provided indirect evidence that normally encountered levels of phytates in cereals and legumes can reduce protein and amino acid digestibilities by up to 10%." (Phytate binding of protein is significant but phytate binding of minerals is of greater significance, nutritionally.) (ref) Higher protein actually helps protect minerals such as zinc and copper from being bound to phytate.
 **Examples of PDCAAS for selected proteins: 1.00 casein (milk protein); 1.00 egg white; 1.00 soy protein; 1.00 whey (milk protein); 0.99 mycoprotein; 0.92 beef; 0.91 soybeans; 0.82 yellow pea; 0.78 chickpeas; 0.76 fruits; 0.75 black beans; 0.73 vegetables; 0.70 Other legumes; 0.59 cereals and derivatives; 0.52 peanuts; 0.42 whole wheat; 0.25 wheat gluten; (from Wikipedia PDCAAS article)

"A comparison of the protein digestibility determination in young (5-week) versus old (20-month) rats suggests greater susceptibility to the adverse effects of antinutritional factors in old rats than in young rats. Therefore, the inclusion of protein digestibility data obtained with young rats, as the recommended animal model, in the calculation of PDCAAS (Protein Digestibility-Corrected Amino Acid Score) may overestimate protein digestibility and quality of products, especially those containing antinutritional factors, for the elderly. For products specifically intended for the elderly, protein digestibility should be determined using more mature rats. "Effects of Antinutritional Factors on Protein Digestibility and Amino Acid Availability in Foods, Gilani et al, 2005. 

Achieving a healthful, complete omnivorous diet is a balancing act; a strict whole plant food diet even more so.


Phytate in whole grains, nuts, legumes: Look for low phytate foods. Try processing by soaking with phytase, either endogenous or added to a phytase poor grain like oatmeal, to release the minerals, but is time-consuming. Or supplement with extra zinc, the mineral most likely to become deficient in high phytate diet. But avoid copper deficiency or interference with magnesium uptake, by avoiding use of an excessive amount. Have serum zinc and copper levels tested. "However, in a balanced diet containing animal protein a high intake of legumes [due to phytate] is not considered a risk in terms of mineral supply." Bioavailability of minerals in legumes, Sandburg (2002)

Oxalates in whole grains, nuts, legumes: Eat lower oxalate foods if possible, for example, pecans rather than almonds or cashews. Soaking or boiling in water helps remove soluble oxalates, or consume with calcium-rich dairy or supplements (calcium helps more than magnesium, but both help limit absorption of oxalates.) Join the Yahoo group, Trying Low Oxalates for up-to-date oxalate levels in a wide variety of foods.

Tannins in skin of nuts, in tea or other sources: Eat only one high tannin-containing meal per day. Eat a copper-rich food and sufficient protein at another meal.

Flaxseed - Limit to one meal per day. Consume enough B6 at other meals. (Do not supplement with pyridoxine. Pyridoxal-5-phosphate is better.)

Vegetables and fat-soluble vitamin supplements: consume with a moderate amount of fat (e.g. extra-virgin olive oil, nuts, avocado etc.)

Cooking increases bioavailability of carotenoids in vegetables. Too much cooking destroys thiamine. See this Self Nutrition Data webpage: Nutritional Effects of Food Processing for effects of freezing, drying, cooking and reheating on nutrient losses. and this document, "6. Effect of processing on nutritional value," produced by Agriculture and Consumer Protection Department of the Food and Agriculture Organization of the United Nations




"Content and bioavailability of trace elements in vegetarian diets" (1994)

Linus Pauling Institute, Micronutrient Information Center – Excellent comprehensive information on Vitamins, Minerals and much more. My main go-to website for everything nutritional.

"Proton Pump Inhibitors: Acid Suppression with a Nutritional Cost" Dana Zallkin

"Vitamin A, D, E & K - How Much and What Type of Fat Do You Need to Absorb These Fat Soluble Vitamins?" SupperVersity blog by Dr. Andro

Self Nutrition Data - the easy way to ballpark the quality of your diet. Register and keep track of the nutrients in your diet.

USDA Nutrient Data Laboratory reports and Databases includes Nutritive Value of Foods, Home and Garden Bulletin No. 72 (HG-72), USDA Reports by Nutrients (link is external), USDA Database for the Flavonoid Content of Selected Foods (2013), Oxalic Acid Content of Selected Vegetables, and Food Composition by nutrients, Macronutrients, Vitamins and Minerals etc.



© 2017 Rochelle Cocco