Thursday, October 27, 2011

Wednesday, October 19, 2011

Phytate Facts

Concerned about phytates in seed foods (nuts, seeds, grains, legumes) blocking mineral absorption and causing ill health?

You can relax.  Context matters. 

Consuming foods rich in ascorbate (vitamin C) with foods rich in phytate can cancel the negative effects of phytate on mineral absorption.[1, pdf]  Just eat some fruits and vegetables with foods that supply phytate.

Some studies have shown substantial degradation of phytate in the human gut (70-86%), indicating that humans adapt to diets high in phytate by increasing small intestinal production of phytase. [2 full text link, 3]

I have never seen any evidence that dietary phytate causes mineral deficiencies except in the context of overall poor quality diet, such as people attempting to live on diets composed entirely of unleavened grains and legume flours without adequate intake of vegetables, fruits, and other mineral sources.

If you live in a modern industrialized nation, when was the last time you had someone tell you that a physician diagnosed her with multiple mineral deficiencies caused by excessive dietary phytate?

I have never seen it.

Anticancer Effects of Phytates

Everything has a front and a back.

According to researchers from Linus Pauling Institute of Science and Medicine, phytates appear to have anticancer effects by binding excess minerals in tissues, depriving tumors of essential minerals.[4 pdf]

Vucenik and Shamsuddin discuss the anticancer properties of phytate in detail; all information and quotes remaining in this post come from their report in the Journal of Nutrition.[5 full text]

Almost all mammalian cells contain phytate in the inositol hexaphosphate (IP6) form and others with smaller numbers of phosphate groups (IP1-5).  When we ingest dietary phytate, intracellular levels of IP6 increase, and from this cells increase the levels of the other forms, which appear involved in "cellular signal transduction, regulation of cell function, growth, and differentiation."

Dietary phytate enters the blood stream and reaches tissues, including tumors, far from the gut.

Tumor cells take up phytate, probably by pinocytosis or receptor-mediated endocytosis.

Phytate inhibits malignant growth in human leukemic, colon cancer, breast cancer, cervical cancer, prostate cancer, and liver cancer cells.

"IP6 inhibited the growth of all tested cell lines in a dose- and time-dependent manner. The growth of cells of hematopoietic lineage was inhibited: human leukemic hematopoietic cell lines, such as K-562 (26,27) and human normal and leukemic hematopoietic cells (27). The antiproliferative activity of IP6 was further reported in human colon cancer HT-29 cells (28), estrogen receptor–positive and estrogen receptor–negative human breast cancer cells (32), cervical cancer (25), prostate cancer (15,33,34), and HepG2 hepatoma cell lines (31). IP6 also inhibited the growth of mesenchymal tumors, murine fibrosarcoma (39), and human rhabdomyosarcoma (38)."
Phytate also causes malignant cells to mature and differentiate into normal cells:
"The potential of IP6 to induce differentiation and maturation of malignant cells, often resulting in reversion to the normal phenotype, was first demonstrated in K-562 hematopoietic cells (26). IP6 was further shown to increase differentiation of human colon carcinoma HT-29 cells (28,29), prostate cancer cells (33), breast cancer cells (32), and rhabdomyosarcoma cells (38)."
Phytates provide an intracellular antioxidant function by binding with iron, which suppresses formation of the most hazardous hydroxyl radicals:
"The antioxidant role of IP6 is known and widely accepted; this function of IP6 occurs by chelation of Fe3+ and suppression of ·OH formation (11). Therefore, IP6 can reduce carcinogenesis mediated by active oxygen species and cell injury via its antioxidative function."
Phytate also stimulates the immune response and protects against carcinogen-induced depression of natural killer cell activity.
"Besides affecting tumor cells, IP6 can act on a host by restoring its immune system. IP6 augments natural killer cell activity in vitro and normalizes the carcinogen-induced depression of natural killer cell activity in vivo (59). "
Phytate only adversely affects malignant cells, not normal cells:
" The most important expectation of a good anticancer agent is for it to only affect malignant cells and not affect normal cells and tissues. That property was recently shown for IP6. When the fresh CD34+ cells from bone marrow was treated with different doses of IP6, a toxic effect (inhibition of the clonogenic growth or as cytotoxicity on liquid cultures) was observed that was specific to leukemic progenitors from chronic myelogenous leukemia patients but no cytotoxic or cytostatic effect was observed on normal bone marrow progenitor cells under the same conditions."
 This indicates that normal cells are adapted to phytate.  Of course, since phytate is abundant in the plant world and also present in almost every mammalian cell.

Phytate inhibits all of the several pathways supporting malignancy:
" From the behavior and characteristics of malignant cells, several principal pathways of malignancy have been established, such as proliferation, cell cycle progression, metastases and invasion, angiogenesis, and apoptosis; interestingly, IP6 targets and acts on all of them."
 In one pilot clinical trial, six patients with advanced colorectal cancer (Dukes C and D) with multiple liver and lung metastasis received oral phytate plus chemotherapy.  One of the patients refused additional chemotherapy after one session and she was treated only with IP6 plus inositol.  What happened?

"...her control ultrasound and abdominal computed tomography scan 14 mo after surgery showed a significantly reduced growth rate. A reduced tumor growth rate was noticed overall and in some cases a regression of lesions was noted."
Say again?  A simple, natural dietary ingredient reversed the progress of cancer!

Which reminds me:
"Pioneering experiments showing this novel anticancer feature of IP6 were performed by Shamsuddin et al. (1820), who were intrigued by the epidemiologic data indicating that only diets containing a high IP6 content (cereals and legumes) showed a negative correlation with colon cancer." 
Most hunter-gatherer groups would have consumed significant phytate from nuts and seeds of various sorts, including legumes.

Dietary Phytate Safety
Vucenik and Shamsuddin agree that chronic phytate ingestion does not cause mineral deficiencies whether gotten from food or isolated form unless the overall diet lacks essential minerals:

"Some concerns have been expressed regarding the mineral deficiency that results from an intake of foods high in IP6 that might reduce the bioavailability of dietary minerals. However, recent studies demonstrate that this antinutrient effect of IP6 can be manifested only when large quantities of IP6 are consumed in combination with a diet poor in oligoelements (6063). A long-term intake of IP6 in food (60,61) or in a pure form (64) did not cause such a deficiency in humans. Studies in experimental animals showed no significant toxic effects on body weight, serum, or bone minerals (Table 5) or any pathological changes in either male F344 or female Sprague-Dawley rats for 40 wk (40,51,52). Grases et al. (65) confirmed our findings and also reported that abnormal calcification was prevented in rats given IP6."
 Phytate has many benefits:  
"In humans, IP6 not only has almost no toxic effects, but it has many other beneficial health effects such as inhibition of kidney stone formation and reduction in risk of developing cardiovascular disease. IP6 was administered orally either as the pure sodium salt or in a diet to reduce hypercalciuria and to prevent formation of kidney stones, and no evidence of toxicity was reported (64,65,79,80). A potential hypocholesterolemic effect of IP6 may be very significant in the clinical management of hyperlipidemia and diabetes (75,76,81). IP6 inhibits agonist-induced platelet aggregation (82) and efficiently protects myocardium from ischemic damage and reperfusion injury (83), both of which are important for the management of cardiovascular diseases. "
Perhaps avoiding and removing phytates from food doesn't serve your best interests?

Perhaps we evolved to consume significant amounts of phytates, and cancer is a disease facilitated by a dietary deficiency of phytates?

Saturday, October 8, 2011

Strength Training May REDUCE Protein Requirements

Conventional wisdom maintains that people engaged in intense strength training have increased protein requirements making it necessary for them to consume more protein than untrained individuals.   I have believed this myself.

I just came across an elegant study by Moore et al [1] which produced evidence that a resistance training program may reduce protein requirements.

The Study Methods

Moore et al put 12 healthy untrained young males (20-24 years old) on a 12 week strength training program described thus:

“The 12-wk whole body resistance training program involved 13 guided-motion resistance exercises divided over 3 different training days, as previously described (8). Briefly, training days were divided into legs (leg press, leg curl, leg extensions, and standing calf raises), pushing exercises (seated military press, bench press, vertical bench press, chest fly, and seated machine triceps extensions), and pulling (latissimus pull-down, seated wide-grip row, seated narrow low row, and seated biceps curl) exercises. One repetition maximum (1 RM) was measured for each exercise before training and 2–4 d after the last training session to evaluate strength changes. Participants trained 5 d/wk at an initial intensity of 70% of the pretraining 1 RM with a goal of 2 sets of 10–12 repetitions during the first 2 wk. In wk 3–12, exercise intensity was adjusted to 80–85% 1 RM so that 3 sets of 6–10 repetitions were performed. All training sessions were supervised by a study investigator to ensure proper technique and exercise intensity adherence. Compliance with the training program in terms of attendance was >95% for all participants.”

Moore et al monitored the results of the training on body composition and protein metabolism using muscle biopsies, nitrogen balance markers (urinary, fecal, sweat and miscellaneous nitrogen losses), and blood assays.  They estimated dietary protein intake using diet records, except for 5 days before and during the final week of training, when the subjects received prepackaged meals of measured protein, fat, and carbohydrate content.  They maintained protein intake constant at ~1.4 g/kg/d for each subject.  Protein intake averaged 109-125 g per day throughout the duration of the study.

Unlike other studies of this type, Moore et al measured protein metabolism in both the fed and the fasting state.


Over the course of the study, the subjects increased strength by 30-90% and gained an average of 2.1 kg bodyweight.  Lean body mass increased by ~2.8 kg (6 pounds) while fat mass decreased by ~0.9 kg (2 pounds). lean mass accrued at a rate of 233 g (~0.5 pound) per week, or 33 g (slightly over an ounce) per day, an amount undetectable on a day to day basis.  Muscle fiber cross-sectional area increased by about 50%.

Moore et al found that this 12-wk training program reduced whole body protein turnover, meaning, the training reduced whole body protein breakdown and synthesis.  Although this might surpise some people, they refer to five studies showing that “resistance exercise is a potent anabolic stimulus that increases the intracellular reutilization of amino acids from protein breakdown in both the fasted and fed states (1,2,28–30). The net result would be that amino acid release from the intramuscular free pool would be reduced with resistance exercise.”

Since protein intake did not change from habitual intakes, they concluded that novice trainees adding significant lean mass do not require additional protein beyond habitual intakes.  They also surmised that since advanced trainees gain lean mass at a much slower rate, or not at all, the protein requirement of an advanced trainee is probably even lower than that of a novice.

In their words:

“Although our data do not directly address the level of protein intake at which zero nitrogen balance would occur, the significantly more positive nitrogen balance after training demonstrates a more efficient utilization of dietary protein in the trained state.”


Moore et al report a very rapid rate of lean mass accrual.  If maintained for 50 weeks in a row, an individual would gain 25 pounds of lean mass.  A subject starting at 150 pounds would end the year weighing 175 pounds, a huge transformation. 

These results suggest that the actual protein requirement for a novice trainee adding 0.25 kg (0.5 pound) lean mass per week lies somewhere below 1.4 g/kg/d.  

How far below? 

Castaneda et al investigated the effect of 12 weeks of resistance training on muscle mass accrual in older adults (average age of 65 years) with chronic kidney disease. [2]   These people consumed a diet providing only 0.6 g protein/kg bodyweight/d, less than half the amount consumed by the subjects of the Moore et al study.  

After 12 weeks of strength training, the subjects showed substantial decreases in markers of inflammation (C-reactive protein and interleukin-6) and substantial increases in strength (about 28%) and muscle hypertrophy (about 23% increase in muscle fiber cross-sectional area).  Considering that these subjects were about 3 times the age of the subjects in the Moore et al study (65 vs. 22 years) and suffering from chronic kidney disease, this 23% increase in muscle cross-sectional area compares very well with the 50% increase found in the Moore et al study.

This study indicates that humans can gain muscle mass on protein intakes as low as 0.6 g/kg/d, which interestingly roughly corresponds to the estimated median protein requirement of 0.65 g/kg/d. [3
Human muscle consists of ~70% water, ~30% protein by weight.  The Moore et al subjects added ~33 g of lean mass daily, equating to adding ~10 g of protein to their musculature daily. 

The Moore et al subjects averaged 62 kg of lean mass at the start of the study and 65 kg at the end. [4

Using the estimated protein requirement of 0.83 g/kg/d [3], ninety-eight percent of individuals starting this program at 62 kg (136 lb) of lean mass would require not more than 50 g of protein per day.  After gaining 2.8 kg (6 pounds) of lean mass, the individual would have 65 kg (143 lb) of lean mass and a protein requirement of not more than 52 g per day.  During the training period, he would require an additional 10 g of protein per day (to accrue 33 g of lean mass daily).  Thus, from start to end, I would estimate his protein requirement as no higher than 60-62 g per day. 

Using the median protein requirement of 0.65 g/kg/d, possibly fifty percent of individuals in the Moore study would require no more than 50 g of protein per day to achieve the results reported.

Since Moore et al report the habitual and controlled protein intake of these subjects as falling between 109 and 125 g per day, by my calculations, the people in this study may have consumed 40 to 60 g excess protein every day, beyond the requirement for building 6 pounds of lean mass in 12 weeks.

According to Moore et al, their 12 subjects required and consumed about 3000 kcal per day. Sixty-two grams of protein provides 248 kcal, which constitutes eight percent of total energy intake.  It would seem possible then that adult physically active humans are adapted to food sources that provide about 8 percent of calories as protein, assuming carbohydrate requirements are met directly rather than through gluconeogenesis.

The following table provides the percent of calories supplied as protein in various foods:

From this it appears that many plant foods, like potatoes, could provide plenty of protein for supporting health and muscle growth if eaten in quantities adequate to cover caloric requirements.

From an evolutionary standpoint, the Moore et al findings make more sense than the idea that strength training increases protein requirements.   

As a general rule,  organisms adapt to demands by resisting the damage those demands inflict.  For example, using your hands for labor will result in callus formation.  Calluses are more resistant to damage than soft skin.  Tanned skin is more resistant to sun damage than pale skin.  Thus, we should expect that the body would respond to heavy physical activity by becoming more resistant to muscle protein degradation and reducing the protein requirements of muscle tissue.

Natural selection would have favored those humans that were most efficient at using available resources. Those who had tremendously increased protein requirements as a result of physical activity would have had to expend more energy on the food quest than those who became more efficient at using protein and deriving protein from less energy expensive resources (i.e. plants vs. animals). Those forced to spend more energy on the food quest would have had less energy left for reproduction; hence they would have left fewer descendants.    

Survival of the most efficient.

Wednesday, October 5, 2011

Dietary Protein, IGF-1, and Hyperinsulinemic Diseases of Civilization

In their paper, “Hyperinsulinemic diseases of civilization: more than just Syndrome X,” Loren Cordain, Michael Eades, and Mary Dan Eades argue that dietary carbohydrate intake, particularly of  refined sugars, promotes hyperinsulinemia, which in turn raises levels of insulin-like growth factor-1 (IGF-1) and androgens, while reducing levels of insulin-like growth factor-binding protein-3 (IGFBP-3) and sex hormone-binding globulin (SHBG).[1]

These endocrine system changes create an environment that promotes cell proliferation and growth, acne, early menarche, epithelial cell cancers (breast, prostate, and colon), increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding.

Effect of Protein Intake on IGF-1: Experimental Results

In “Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans,” Fontana et al report on their studies of the effect of either caloric restriction or protein restriction on these endocrine markers in humans. [2]

In one study, they compared the effects of three interventions:

1) 20% caloric restriction with no change in energy expenditure (CR)
2) 20% increase in energy expenditure with no change in caloric intake (EX)
3)  healthy lifestyle control group with no specific manipulation of energy balance (HL)

All three groups consumed diets supplying about 16% of energy as protein. 

After one year, although both the CR and the EX interventions produced substantial and similar changes in body mass (~ 6 kg lost) and body fat percentage (~ 23% decrease), neither intervention reduced levels of IGF-1 or increased IGFBP-3.  This contrasts with rodent studies, wherein caloric restriction does reduce IGF-1 and increase IGFBP-3.

In the second study, they compared the IGF-1 and IGFBP-3 levels in members of the Caloric Restriction Society (CR) who had been practicing caloric restriction for an average of 6 years, with those of age-matched controls consuming a typical Western diet (WD).  The CR group averaged only 1800 kcal per day with 24% of energy from protein and 28% from fat, while the WD group averaged 2500 kcal per day with 16% from protein and 34% from fat. 

Thus, the CR group averaged 108 g of protein daily, and the WD group 100 g of protein daily, both at least twice the required amount for a 150 pound male.

They reported: 

“As in our 1-year CR study, we found that there were no differences in serum IGF-1 and IGFBP-3 concentrations, and IGF-1 : IGFBP-3 ratio between the CR and Western diet groups.... These data provide evidence that, in contrast to the decrease in IGF-1 in rodents, a reduction of IGF-1 expression is not a component of the adaptive response to long-term CR in humans.”

In contrast to these findings, Fontana et al note that fasting for 10 days markedly reduces IGF-1 into the range found in growth hormone deficient patients, and this correlates closely with the excretion rate for urea, a marker for nitrogen balance and thus protein intake.

Consequently, Fontana et al did a third study “comparing the serum IGF-1 and IGFBP-3 concentrations, and IGF-1 : IGFBP-3 ratio in 28 vegans who had been consuming a moderately protein-restricted (PR) diet (0.76 g kg−1 per day; ~10% of intake from protein) for ~5 years age-matched with 28 members of the Calorie Restriction Society who consume a high-protein diet (1.73 g kg−1 per day; ~24% of energy intake from protein).” 

The vegan/PR group had an average protein intake of 50 g per day, while the CR group averaged twice as much, 106 g per day.

Fontana et al found that “Both serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio were significantly lower in the moderately PR diet group than in the severe CR diet group, whereas fasting insulin and C-reactive protein were similarly low in the moderately low-protein vegan and CR groups.’

In other words, the vegan/PR group had the most favorable IGF-1 and IGFBP-3 levels, while also having low serum insulin and C-reactive protein comparable to the CR group, without enduring caloric restriction.

This table compares the values of the PR group to the CR group:

The low protein group had an IGF-1 level 21% lower than the low calorie group

Of interest, the “serum total and free IGF-1 concentrations were lower in the moderately PR group than in the severe CR high-protein diet group, despite the PR groups’ higher body weight, BMI and body fat content.”

This raised the possibility that the higher protein intake of the CR group prevented desired declines in IGF-1, so Fontana et al performed a fourth study.  They had 6 CR volunteers to reduce their protein intake from 1.67 g/kg per day to 0.95 g/kg per day, a 43% reduction, while maintaining caloric intake constant.  The 0.95 g/kg/d level of intake still exceeds the reference daily intake of 0.83 g/kg/d, which covers the needs of 98% of the population.

As a result of this reduction of protein intake, the CR volunteers had an average 25% reduction in IGF-1 levels, confirming the hypothesis that high protein intake prevents reduction of IGF-1 levels even in the context of caloric restriction.

This then suggests that high protein intake may raise IGF-1 levels and thus promote all the diseases that Cordain, Eades, and Eade linked to elevated IGF-1 and androgens and reduced IGFBP-3 and SHBG: acne, early menarche, epithelial cell cancers (breast, prostate, and colon), increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding.

Another question arises from this research:  Since the vegans had lower IGF-1 levels than the omnivorous CR group, and plant proteins have different amino acid profiles than animal proteins, I wonder if plant protein has a different effect on IGF-1 than animal protein?

Who eats a high protein diet?

Most people do not understand that the reference daily intake (RDI) is not a minimum requirement.  In fact, the RDI for protein, 0.83 g/ kg of body weight per day, is calculated to cover the needs of the people in the 98th percentile of requirements.

Many people require substantially less protein than the RDI.  The median requirement for the general population  actually only amounts to  0.65 g/kg per day, about 20% less than the RDI.  [ 4 ]

For a 150 pound (68 kg) male with 10% body fat, this translates to a requirement of 40 to 50 g of protein daily.  NHANES data suggests that half of U.S. males consume 40% more than the RDI level of protein, which means that many consume more than twice as much protein as they actually require.[5

When I ate a meat-based paleo diet, my protein intake ranged from 130 -190 g per day, two to four times the maximum requirement of someone with my bodyweight; which according to human protein requirements research [6] amounts to an excessive protein intake. 

According to this research, I probably had an elevated IGF-1 level and ratio to IGFBP-3.