Phosphorus, the Magic Bullet For Fat Loss and Against the YoYo-Effect? P. Restores Thermogenesis, Enhances Satiety

This is not the first study to suggest that as little as 12.5% of the suggested upper limit for phosphorus can make a big difference when it comes to weight loss and the ease of weight loss when you battle reduced diet-induced thermogenesis & increased appetite.

I guess those of you who have been reading every SuppVersity article will remember my January article "Phosphorus, an Anti-Obesity Agent? 3x375 mg With Each Meal Strip Almost 4 cm Off Obese Waists in Only 12 Weeks" (re-read it). You liked that one? Well, I guess you will also like the fact that the evidence that there's some use in phosphorus supplements is accumulating.

Recently, scientists from the Lebanese American University in Beirut, Lebanon (Bassil. 2016), have observed that "P supplementation recovers the blunted diet-induced thermogenesis in overweight and obese subjects and enhances their postprandial satiety" (Bassil. 2016).

Phosphates have also been touted as buffer for athletes, but apper less effective than NaHCO3:

The Hazards of Acidosis

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HIIT it Hard W/ NaCHO3

Creatine + BA = Perfect Match

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Yes, that's right: This means that phosphorus aka "P" supplementation will address two of the main reasons for weight regain aka the YoYo-effect - a diet- / weight-loss-induced reduction in diet-induced thermogenesis and a decrease of the satiety effects of the foods you consume.

Since diet-induced thermogenesis (DIT) is believed to be largely related to ATP production, which is dependent on phosphorus (P) availability, Bassil and Omar speculated that supplementing extra phosphorus to lean and overweight/obese healthy subjects should have beneficial effects on their diet-induced thermogenesis. Accordingly, they measured the latter with or without P in 10 lean and 13 overweight/obese adults in a double-blind randomized cross-over pilot study with a one week washout period that was meant to exclude any possible interference of the previous trial.

Figure 1:  Diet-induced thermogenesis after drinking 75 g glucose solution with and without phosphorus supplementation in lean and obese subjects. (A) Resting metabolic rate at baseline and over 3 h (180 min) after drinking 75 g glucose solution in lean and obese subjects with phosphorus (solid lines) or placebo (dashed lines); (B) Total area under the curve of RMR with phosphorus (solid bars) or placebo (dashed bars) in lean and obese subjects (Bassil. 2016).

The "problem" is that the subjects were healthy, sedentary non-smokers whose body weight had been stable for the past 3 months. As I will elaborate in the bottom line, the significance of the results for reduced-obese individuals, i.e. people who have lost a significant of body weight and are now facing an increased risk of yoyo-ing backup, is limited... but as I said: more about that later.

Correlation between daily dietary P intake and subjects' BMI (Bassil. 2016).

Additional evidence: Phosphorus intakes correlate negatively with BMI -- Next to the previously cited study by Ajoub, et al. (read more), the study at hand does also provide additional evidence that high(er) phosphorus intakes could have an obesity protective effect. After all, the data in the figure to the left clearly indicates that there is a linear, inverse correlation between obesity / BMI (in normal people a good measure of obesity) and the individual's habitual phosphorus intakes. Since fasting serum P is tightly controlled in healthy humans and is not affected by diet, so that the effect of dietary P is only evident post-prandially, this differential DIT response of lean and obese individuals (see Figure 1).

Speaking of explanations... a 2006 study by Mataix, et al. shows that Spaniards who consume more energy than they'd need have an increased risk of suboptimal phosphate intakes. The same goes for people with low education (Mataix. 2006). Both could point to phosphate intakes as a correlate not a cause of reduced obesity risks. Furthermore, we must not forget that US citizens with the highest phosphorus intakes happen to have an increased risk of mortality (Chang. 2014). This association with mortality risk, however, well be unrelated to phosphorus and a simple result of the high amounts of phosphates you will also find in processed foods. In this case, phosphorus would rather be a marker of increased junk food intake, which in turn could be the actual reason for an increase in mortality risk - an increased risk that may, however, eventually be a result of a messed up balance between phosphorus, calcium and magnesium.

I the study at hand, the DIT, as well as the subjects' resting metabolic rate, respiratory quotient, and substrate utilization (ratio of fat and glucose oxidation) were measured after a 10 h overnight fast at fasting and every 30 min for 3 h after subjects drank a standardized glucose solution, with P (500 mg from potassium phosphate, 23% monobasic and 18% dibasic | considering the results of previous studies, it is, by the way, unlikely that the potassium in KP did the trick) or placebo (cellulose) pills.

Figure 2: Subjective appetite scores of lean (gray) and obese (black) subjects, 3 h after drinking 75 g glucose solution with phosphorus (solid bars) or placebo (dashed bars) supplementation (Bassil. 2016).

To assess the subjects' hunger/satiety response, the researchers used the classic validated visual analog scale (VAS) questionnaires we all know from other studies - with quite intriguing results.

• Overweight/obese subjects had a blunted DIT with placebo. 
• P supplementation induced a 23% increase in their DIT area under the curve (p < 0.05).
• The increase in DIT was associated with an increase in carbohydrate oxidation. 
• All subjects, obese or lean had lower appetite following P supplementation.
• The decrease was expressed as a significantly (p = 0.02) lower desire to eat a meal (4.0 ± 0.7 cm) compared with placebo (5.8 ± 0.9 cm). 

At least during/before a diet, the co-consumption of phosphorus with glucose-containing meals could thus, as the scientists point out, be a valid means to recover the blunted diet-induced thermogenesis in overweight and obese subjects and enhances their postprandial satiety.

High phosphorus intakes and/or supplementation accelerated the fat loss in a previous study sign.

So, will this actually prevent the YoYo-effect? That is possible, but nothing the study at hand can prove. Rather than that, it provides new evidence of the usefulness of phosphorus supplements during weight loss interventions. A usefulness that has been previously confirmed by Ajoub, et al. (read more), but does not necessarily mean that the same beneficial effects will be observed in reduced-obese (=formerly obese) individuals whose DIT and appetite response have been shown to be significantly depressed in the post-dieting period. Until this study has been done, we still have the evidence of its usefulness for overweight individuals trying to shed body fat.

Everyone? Well, I guess another two qualifications have to be made: (a) If the effect is, indeed, as the scientists speculate, mediated by ATP, it is not unlikely that the benefits depend on the co-consumption of glucose or rather carbohydrates. Accordingly, low carbers may benefit less, maybe even not at all. And (b) low carbers have another "disadvantage" with respect to phosphorus supplementation: With plenty of the foods you see in the photo at the top-right, their phosphorus intake usually is already very high - increasing it, even more, may thus have no effect irrespective of the glucose intake. Plus: Eventually, you must keep an eye on the balance between phosphorus, calcium, and magnesium. While a healthy kidney helps to balance serum imbalances out, adding another 1,500 mg of phosphorus or 37,5% of the upper intake limit for phosphorus (4g/day) to your diet with the 500mg extra phosphorus you'd take with e.g. three daily meals could increase your long-term calcium and magnesium requirements to a certain degree - a degree that you will probably cover automatically if you get your phosphorus from foods, not supplements, because only the former (e.g. dairy) come packaged with all important co-factors | Comment!

References:

• Bassil, Maya S., and Omar A. Obeid. "Phosphorus Supplementation Recovers the Blunted Diet-Induced Thermogenesis of Overweight and Obese Adults: A Pilot Study." Nutrients 8.12 (2016): 801.
• Chang, Alex R., et al. "High dietary phosphorus intake is associated with all-cause mortality: results from NHANES III." The American journal of clinical nutrition 99.2 (2014): 320-327.
• Mataix, José, et al. "Factors influencing the intake and plasma levels of calcium, phosphorus and magnesium in southern Spain." European journal of nutrition 45.6 (2006): 349-354.

Phosphorus, an Anti-Obesity Agent? 3x375 mg With Each Meal Strip Almost 4 cm Off Obese Waists in Only 12 Weeks

You knew that all these fat burning high protein foods are high in phosphorus?!

1 cm per week? What sounds like an advertisement for the next best useless fat burner, is in fact the rate at which the 47 obese, but otherwise "healthy" subjects in a recent study from the American University of Beirut had to tighten their belts (Ayoub. 2015)... Ok, I know that this is not DNP-like earth-shatteringly fast, but in view of the fact that the placebo group had to loosen their belts to accommodate for an additional 0.36 cm increase in waist circumference, it is still quite amazing. I mean, would you have expected that the amount of phosphorus of ca. 300 g salmon would have such an effect if there's no other difference in diet or physical activity between the two groups of overweight participants?

If you're looking for a true fat burner, try coffee ;-)

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Speaking of which,... there were 47 participants (placebo group n = 21; phosphorus group n = 26), 16 men and 31 women, who completed the intervention over the course of all subjects were requested to take three tablets that contained either 375 mg phosphorus or a placebo (Nutricap Labs, Farmingdale, NY, USA) with each main meal (breakfast, lunch and dinner) for 12 weeks (there were no detectable differences in size or weight between intervention and control envelopes | see Table 1).

Table 1: Overview of the baseline characteristics of the subjects in the placebo and phosphorus group (Ayoub. 2015).

Otherwise, the subjects had to maintain their regular dietary and (sedentary) physical activity habits. Whether this was actually the case, however, was unfortunately not monitored by the scientists -- I know that's a bummer, but it is (a) very unlikely that the subjects suddenly started to work out, when they were asked not to, and (b) unrealistic to assume that any effects on the diet that would not be a consequence of the phosphorus supplementation would occur only in the treatment, but not in the active treatment group. Changes in dietary intake that may have occurred in response to the phosphorus treatment, on the other hand, must be expected to occur in the real world as well and would thus only add to the practical relevance of the study at hand compared to a study, where the diet was standardized and potential effects on appetite intake could not have been measured, anyway (as we are going to see further down, this is actually an important fact, even though it would still be nice if we had at least data from food logs).

Figure 1: Weight, waist circumference and serum phosphorus levels expressed rel. to baseline (Ayoub. 2015).

If you look at the selected study outcomes in Figure 1 (please note the non-existing effects on serum phosphorus!), it is still sad that Ayoub et al didn't at least tell their subjects to run food logs, because now everything we have as a basis to speculate about the mechanism that triggered the 'weight and waist loss' are the highly unreliable appetite scores in Table 2; and the latter clearly suggest, but certainly don't prove that the effect was the result of a mere reduction in energy intake.

Table 2: Changes in subjective appetite scores from baseline to 12 weeks (Ayoub. 2015).

Since we don't have those food logs, though, we will have to rely on older studies and a few assumptions to make sense of the results. Well, then...

• there's firstly the evidence from observational studies linking high protein, high dairy and high whole grains intakes to reduced risk of overweight and metabolic syndrome - since a high intake of all three of these food groups is also associated with an increased intake of phosphorus, that's the first line of evidence which supports a mechanistic role of increased phosphorus intakes in weight management,
• there's secondly epidemiological evidence showing an inverse association between an individuals phosphorus status and his or her body weight and waist circumference, and 
• there's thirdly the well-known effect of phosphorus on ATP production, especially in the liver, of which previous studies suggest that it regulates afferent neural signals to the central nervous system which will result in a reduction in food intake (Friedman. 2007).

If we take all three lines of evidence into consideration, we are yet back to square one: the most likely, but unproven mechanism by which the addition of phosphorus to the diet helped the obese subjects in the study at hand lose weight is a reduction in energy intake.

Figure 2: In a previous study the addition of 500mg of phosphorus to a non-caloric or caloric pre-load has already been shown to significantly reduce the food intake during ad-libitum (pizza) lunch (Obeid. 2012).

The latter, by the way, is not just in line with the subjective appetite ratings of Ayoub's study participants, but also with the results of a previous study by Obeid et al (2012), in which the addition of phosphorus to a water, sucrose, fructose + glucose, or pure glucose preload that was administered before an ad-libitum meal lead to an additional attenuation of food intake (see Figure 3). Against that background it is actually very reasonable to assume that the same effect, i.e. a mere reduction in energy intake, is responsible for the 'weight and waist loss' in the study at hand, too.

If you're a loyal SuppVersity, you will probably remember that phosphorus supplements have also been shown to ameliorate the decrease of the active thyroid hormone T3 dieters experience as they progressively reduce their food intake | learn more

Disappointed that it all comes back to eating less, once again? I know the mechanism, a reduction in food intake, is not exactly exciting. It means, after all, that you can still not eat as much junkfood as you want and stay lean if you only supplement with enough phosphorus (in view of the potential diarrhea you may get from very high doses, I suspect you could eat as much as you want... but you certainly don't want to ;-).

With the previously reported beneficial effects of phosphate supplements against the metabolic slow down in response to significantly reduced energy intake, the study at hand does yet contribute another line of evidence that suggests that our diet may eventually not really be so much too high in phosphorus / -phates as we believe it was | Comment!

References:

• Ayoub et al. "Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical trial." Nutrition & Diabetes (2015) 5, e189; doi:10.1038/nutd.2015.38.
• Friedman, Mark I. "Obesity and the hepatic control of feeding behavior." Drug News Perspect 20.9 (2007): 573-8.
• Obeid, O. A., S. Dimachkie, and S. Hlais. "Increased phosphorus content of preload suppresses ad libitum energy intake at subsequent meal." International Journal of Obesity 34.9 (2010): 1446-1448.

Science Round-Up Seconds: The Macro-Mineral Alphabet & the Potential Health Hazards of Diet-Induced Latent Acidosis

You lose 600x more sodium than magnesium during a workout. The RDA is yet only ~3-4x higher (Montane. 2007).

If you already listened to the podcast of yesterday's installment of the SuppVersity Science Round Up (if you have not already done so, you can dowload the podcast, here), you may have noticed that I confused the minimal potassium (K) to sodium ratio (Na), which is probably ~1:1, and the "original" K:Na ratio in the "paleo diet".

According to Sebastian et al. (2002) the latter is ~8-9:1 in other words: 8-9 mols of potassium per mol of sodium. That's miles apart from the 1:2-3 ratio the average Westerner (the exact ratio varies depending on which study you refer to) uses as a springboard to hypertension ;-)

The (un-)definite mineral synergism/antagonism chart

Another thing you may have noticed with yesterday's show is the fact that the show was pretty "topic centered". My personal feeling is that it has a much better flow this way and that not despite, but because Carl and I did not cover such a broad range of topics. I cherish the hopefully non-futile hope that you feel the same but am obviously open for any constructive criticism from your side

The SuppVersity macro mineral chart provides a general overview of the complex interactions that exist between calcium, phosphorus, magnesium, sodium, chloride, and potassium (compiled based on various sources)

. This, by the way, does also apply to the corresponding installment of the Seconds, of which you will soon realize that it is not a non-related add-on, but will expand, explain and summarize interesting aspects we've covered in the live show (note: from next week on the Science Round-Up will air at 12 PM EST, the same URL as usual).

On that note, let's start with an "expansion" I already promised to deliver towards the end of the show: some information on the synergism and antagonism of the macro minerals. It's a pretty complex matter and the following illustration is based on generalizations. Some of them, like the low-level exception to the antagonism between calcium and magnesium, of which I believe that it is important to know are explicitly mentioned, others are not.

A very good example of the former, i.e. the important second order interactions is the influence sodium has on the antagonism between potassium and magnesium. The latter disappears, when sodium levels are high and magnesium is needed as a sodium antagonist. Similarly, the often-touted antagonism between magnesium and calcium is actually a co-factor relation, where any "antagonism" is only the result of imbalances between the two.

The good, the bad and the ugly: Just a question of the "wrong" perspective

One thing that should actually be obvious, but is often ignored in all the hoopla about the "good" and "bad" guys among the macro-minerals is that "antagonisms" do not contradict the essential nature of all of the electrolytes, which are - antagonistic or not - in the end, all actors in the same metabolic play.

Figure 1: Average ratio of mineral content (new:old) of 20 vegetables and 20 fruit: data based on comparison of  UK Government’s Composition of Foodsdata at two-time points separated by approximately 50 years (Mayer. 1997)

I mean, take calcium and phosphorus as an example, they are both essential for the structural integrity of your bone and the fact that calcium has a reputation of being the "good guy", while phosphorus is the "bad guy" is just a necessary consequence of the overabundance of the latter, i.e. phosphorus from grains, soft drinks, dairy products, meats, fish, seeds, nuts, eggs and due to the change in mineral ratios (cf. figure 1) even most fruits and vegetables in the food chain of Mr. Joe Average, these days.

According to a 2009 paper by Dana Cordell et al. this may well change in the not all too distant future, after all "the quality of remaining phosphate rock is decreasing and production costs are increasing" (Cordell. 2009). With estimates saying that the demand for phosphorus is going to double within the next 40 years, it stands to reason that the decried overabundance of phosphorus, which is, among other things, also responsible for lowering the zinc content of the produce (cf. Peck. 1980) may be partly reversed within the next decades... I mean, we all know that nothing is as "convincing" as with financial interests, right?

The strong ion difference determines your pH levels

What's the difference between macro-minerals and their "little brothers" the trace minerals? Calcium, sodium, potassium, phosphorus, magnesium, chloride and sulfur are macro-minerals because you need them in amounts that are greater than 100mg per day. Of the trace minerals, on the other hand, you need less (in most cases much less) than 100mg per day. That does not mean though that Iron, zinc, copper, chromium, fluoride, manganese, iodine, molybdenum and selenium were less important - it's merely a quantitative distinction.

While it stands to reason that there is a reason, calcium, sodium, magnesium, and potassium are also called "electrolytes", astonishingly few people can actually give an ad hoc explanation why this is the case - and that despite the fact that their lives depend... no, not on the answer, but on the existence and physiological function of electrolytes ;-)

If you have listened closely to your physics teacher, you will yet probably be aware that an "electrolyte" (electro- ~ charge, -lyte ~ carrier) is a positively or negatively charged molecule (ion) and nothing out of the ordinary in nature.

In your body electrolytes are used to establish ionically charged gradients, similar to the gradient that exists between the positive and negative pole of a battery. These gradients are situated on the cell membranes in excitable tissues, such as muscle and verve, where they facilitate or hinder the influx/efflux of other charged particles.

One of these gradients, in fact probably the physiologically most significant one, by the way, is established by positive sodium (Na+) and potassium (K+) ions and their negative counterpart chloride (Cl-) - exactly those electrolytes you've heard about in yesterday's show (remember: whenever you hear "salt" it actually means Na + Cl).

The electrolytes are not the only charged particles ...

From your chemistry lessons, you may remember that there are not just ionic atoms, but also ionic molecules and that the electron configuration of these particles will determine how they bind, interact and react. But I guess, we have had more than enough complicated theory for today, so if you want to know how the anions and how the strong ion difference (SID) is calculated, check out this brief overview over at acid-base.com.

Rather than going into the details of the mechanism, I decided that it would probably of greater value to wrap the Seconds up with a brief overwiev of the downstream effects of a metabolic state, of which Pizzorno, Frassetto and Katzinger point out that it is not necessarily characterized by acedemia, i.e. pH levels below the "magic" (if we were honest, we'd you'd have to write arbitrary, here) cut-off limit of pH 7.35:

High intensity exercise can also lower your blood pH, an effect you can counter with sodium bicarbonate

"Acidosis only becomes acidaemia when compensatory measures to correct it fail. To illustrate the difference between acidosis and acidaemia, take the following example: two processes occurring simultaneously in the same individual, such as a respiratory acidosis combined with a metabolic alkalosis. In this case, if the respiratory trend toward acidosis is greater than the metabolic trend, a pH of less than 7·35 may be reached, and would be considered acidaemia, despite the presence of a metabolic alkalosis. The intensity of each ‘process’ will determine the pH, but the terms themselves (acidosis, alkalosis) do not indicate a certain pH." (Pizzorno. 2009)

In other words, you don't have to suffer from diabetic or otherwise pathogenic "acidosis", to suffer from one of the following ill health-consequences:

• 

  Hip fracture incidence per 100,000 study participants; aggregated data from cohorts from 33 countries (Frassetto. 2001)

  Calcium loss, bone loss, osteoporosis - Unfortunately, this is not only the best-known side effect of "being too acidic", it's also the only one people take seriously. In that, scientists and lay press alike have zoned in on the high intake of animal proteins as the main confounding factor. But despite the fact that the high sulfur content (methionine, cysteine & co) does certainly contribute to the problem, the data in the figure at the right should make it quite clear that the stuff we eat and don't eat with our meats is at least as much to blame for the misery. In view of the fact that
  

  "[...] cereal grains themselves are net acid-producing and alone accounted for 38% of the acid load yielded by the combined net acid-producing food groups in the contemporary diet" (Sebastian. 2002)

  the average (processed) grain addicted US citizen with his/her quasi-non-existent vegetable intake would end up way on the left side of the x-axis of the graph on the right-hand side, even if he ate not a single gram of animal protein - we would just have to relabel the axis to vegetable/acidd forming food intake (including grains!)".
• Increased renal nitrogen excretion and hampered protein synthesis - One of the less known effects of an increased acid/base ratio is an increase in nitrogen excretion that will obviously not simply hamper your gains, but can also set you up to sarcopenia (age-induced muscle loss).
  
  

  

  Correcting a diet-induced low grade metabolic acidosis with K-bicarbonate reduces the nitrogen loss of 750mg - 1000mg per day (per 60kg BW) in post- menopausal women (Frassetto. 1997)

  In the end, the excretion of nitrogen is nothing, but an adaptive mechanism and a consequence of the catabolism of tissue protein. It is, if you will, a basic necessity for your body to rob your muscle and other tissue of glutamine and all other amino acids, that can be convert to glutamine in the liver, from where it is delivered to the kidney where it's used to synthesize ammonia and excrete the potentially toxic acid load. This will obviously mitigate the severity of the acidosis, it does yet also entail a net loss in muscle and organ protein that cannot be compensated for by an increase in acid forming protein in your diet.
  
  As the data in the figure to the right goes to show you this is a process that's regulated on a day to day basis and the relief in nitrogen loss (data in mg/day/60kg) provided by bicarbonate supplementation (days 0-18) is transient and disappears as soon as you return to your regular low-base, high acid diet (days 19-30).
• Impairments of the growth hormone / IGF-1 axes - Brunnger et al. tested in 1997 whether experimental acidosis would have an effect on the growth hormone / IGF-1 axis and observed a "significant decrease in serum IGF-1 concentration without a demonstrable effect on IGF binding protein 3", which points towards an acid induced "primary defect in the growth hormone/IGF-1 axis" that occurs "via an impaired IGF-1 response to circulating growth hormone with consequent diminution of normal negative feedback inhibition of IGF-1 on growth hormone" (Brunger. 1997). Interestingly, Mahlbacher et al. were able to show that the administration of IGF-1 can in turn ameliorate acidosis and thus correct the previously discussed nitrogen wasting (Mahlbacher. 1999).
  
  

  

  Learn more about the effects of GH, IGF1 and it's splice variants MGF & co and their influence on skeletal muscle hypertrophy in the respective part of the Intermittent Thoughts on Building Muscle (go to the overview).

  In fact, potential physiological effects of the acid-induced impairment of the GH / IGF-1 axes had been observed much earlier, already. McSherry et al. for example report in a 1978 article in the Journal of Clinical Investigations that children with short stature and classic renal tubular acidosis developed normally, when they were treated with adequate amounts of alkalizing agents.
  
  That similar negative effects can be observed even in the presence of "low-grade 'tonic' background metabolic acidosis" was confirmed by Frassetto et al. who observed statistically significant increases (+11%) in 24-hour mean growth hormone secretion in post-menopausal women with diet-induced low-grade metabolic acidosis, when their dietary acid load was neutralized with adequate amounts of potassium bicarbonate (Frassetto. 1997).
  
  In a subsequently published study the scientists argue that the concomitantly observed increases in osteocalcin and bone metabolism would confirm the physiological significance of these changes (Frassetto. 2001). The effects on bone add to the well-known beneficial metabolic effects of growth hormone ( and line up with the recently reported association between low growth hormone levels and memory impairments (Wass. 2010).
  
  In view of the bad press GH and IGF1 are getting, it is important to point out that we are talking about a normalization of the GH/IGF-1 axis, here. It is therefore unlikely that the restoration of a normal acid-base balance will have any of the anti-longevity and pro-cancerous (see next bulletin point) effects of growth hormone and IGF-1 you may have read about in the pertinent literature.
• Potential protective / anti-cancer effects - While conclusive scientific evidence for the involvement of low-grade acidemia in the etiology of cancer is still missing, it has long been speculated that the genetic and epigenetic perturbations, which will turn normal cells into cancer cells may be triggered (among other factors) by disturbances in the acid-base equilibrium. As Ian Forrest Robey points out in his 2012 review of the literature, a diet induced
  

  "[a]cid-base disequilibrium has has been shown to modulate molecular activity including adrenal glucocorticoid, insulin growth factor (IGF-1), and adipocyte cytokine signaling, dysregulated cellular metabolism, and osteoclast activation, which may serve as intermediary or downstream effectors of carcinogenesis or tumor promotion." (Robey. 2012)

  If you want to learn more about the "state of the art research" on the potential link between latent dietary acidosis and the development of cancer, I suggest you simply read the free fulltext of the paper on PubMed. 

I guess, now that you've learned about some of the intricacies of adequate mineral intakes and balances, the acid / base balance, nitrogen and bone loss, growth hormone and cancer, and listened to the interactions of sodium blood pressure, blood glucose and insulin on yesterday's show, it's about time to come back to the simple things that work - the bottom line, so to say...

"What was that about the nutrient sufficiency of the vegetarian / vegan diet, you said on the air?" The above figure shows the % of omnivores, vegans and vegetarians who meet the RDAs  for protein and fiber and selected vitamins and minerals (DiMarino. 2013)

Bottom line: A whole foods convenient-"food" free with the right balance of vegetables, protein, and a reasonable amount of complex largely unprocessed carbohydrates, fats and fruits - call it "ancestral" or "paleo", if you will - is going to provide you with all the minerals you need, it will contain them in the right ratios and supply your body with all the co-factors it needs to use them. It will stabilize your pH levels, normalize your growth hormone / IGF-1 axis and is beyond any doubt the most effective way to get and stay in shape, to reduce your cancer risk, ward off diabetes and lead a life that's not simply long, but also worth living.

If you adhere to these simple rules, there is no reason to be worried about "not getting your minerals" and other essential nutrients. After all, this is what distinguishes you from the "average" western omnivore, vegetarian or vegan who fails to meet most of his or her nutrient requirements.

References:

• Brungger M, Hulter HN, Krapf R. Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis: new cause of growth hormone in sensitivity in humans. Kidney Int. 1997; 51:216–221
• Cordell D, Drangert J-, White S. The story of phosphorus: Global food security and food for thought. Global Environ Change. 2009;19(2):292-305.  
• DiMarino A. A Comparison Of Vegetarian Diets And The Standard Westernized Diet In Nutrient Adequacy And Weight Status. The Ohio State University. A Thesis Presented in Partial Fulfillment of the Requirements for Graduation with Distinction from the School of Health and Rehabilitation Sciences of The Ohio State University. 2013. 
• Frassetto L, Morris RC, Jr., Sebastian A. Potassium bicarbonate reduces urinary nitrogen excretion in post-menopausal women. J Clin Endocrinol Metab. 1997: 82:254–259.
• Frassetto L, Morris RC Jr, Sellmeyer DE, Todd K, Sebastian A. Diet, evolution and aging--the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Eur J Nutr. 2001 Oct;40(5):200-13.
• Mahlbacher K, Sicuro A, Gerber H, Hulter HN, Krapf R. Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans. Metabolism. 1999; 48:763–770
• May RC, Kelly RA, Mitch WE. Metabolic acidosis stimulates protein degradation in rat muscle by a glucocorticoid-dependent mechanism. J Clin Invest. 1986. 77:614–621.
• Mayer AM. Historical changes in the mineral content of fruits and vegetables. British Food Journal. 1997; 99(6):207 - 211
• McSherry E, Morris RC, Jr. At tainment and maintenance of normal stature with alkali therapy in infants and children with classic renal tubular acidosis. J Clin Invest. 1978; 61:509–527. 
• Montain SJ, Cheuvront SN, Lukaski HC. Sweat mineral-element responses during 7 h of exercise-heat stress. Int J Sport Nutr Exerc Metab. 2007 Dec;17(6):574-82.
• Peck NH, Grunes DL, Welch RM, MacDonald GE. Nutritional Quality of Vegetable Crops as Affected by Phosphorus and Zinc Fertilizers Agron. J. 1980; 72: 528–534.
• Pizzorno J, Frassetto LA, Katzinger J. Diet-induced acidosis: is it real and clinically relevant? Br J Nutr. 2010 Apr;103(8):1185-94.
• Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris RC Jr. Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors. Am J Clin Nutr. 2002 Dec;76(6):1308-16.
• Wass JA, Reddy R. Growth hormone and memory. J Endocrinol. 2010 Nov;207(2):125-6.
• Williams B, Layward E, Walls J. Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis. Clin Sci. 1991; 80:457–462

Hypothesis: Does Vitamin D "Deficiency" Protect Us From Phosphorus Overload? 1,25OHD Production Drops by 19pg/dL With Each 1mg/dL Increase in Phosphorus

Image 1: Did you ever take into consideration that your body may refuse to produce vitamin D with good reason?

Do you know that? You have an idea, a hypothesis, a stroke of genius, but for whatever reason you don't have access or time to do some research to probe it!? For me that was the case with my "phosphorus <> vitamin D" hypothesis. And in view of the fact that I started to ignore the dozens of weekly papers on the great importance vitamin D, by the means of which their authors obviously hope get their share of the sudden media attention, it took a more or less unrelated post by Mallory Pazdersky on Highbrow Paleo about the paradoxically low vitamin D levels of astronauts to remind myself that I wanted to do some research in this area... and what should I say? It did not take very long to find evidence in support of my theory.

Hypothesis: Our bodies reduce vitamin D to cope with the high phosphorus load in our diets

Don't get me wrong, I don't have the hubris to claim that this is the one and only explanation for the prevalence of "low" vitamin D levels in our society, but if you take a look at the experimental evidence from a 1986 study by Portale et al. (Portale. 1986; cf. figure 1), you will have to admit that the 1,25(OH) vitamin D levels (unfortunately similar data for 25OHD does not exist), you see in the "high phosphorus" weeks towards the end of the 30-day study period, in the course of which the subjects received diets that contained normal (1,300mg), low (<500mg/day) and high (3,000mg) amounts of dietary phosphorus, is highly reminiscent of the pattern the aforementioned busybodies are mourning in their papers.

Figure 1: Effects of restriction (<500mg/day, total) and supplementation (3,000mg/day) phosphorus on serum phosphorus and vitamin D levels in six healthy men (ages 26-40y); left- group average, right - individual response (Portale. 1986)

While the vitamin D levels of the the six health men (age 26-40y) hover at the lower end of the normal range in the "normal" diet phase, there is a rapid increase up to 65-75pg/dL in response to the reduced phosphorus intake in the "low phosphorus" phase of the trial (<500mg/day); an increase, which drove the vitamin D levels right to the top of the normal lab range. The high phosphorus diet (3,000mg/day), on the other hand, had the vitamin D levels plummet to a level hardly above what even official guidelines would consider full-blown deficiency.

Note: The rise in phosphorus and drop in vitamin D in the Portale study happened in the presence of adequate intakes of the phosphorus "antagonists" magnesium (350mg/day, which is 100mg more than the average American is getting from his / her diet; cf. Ervin. 2004) and calcium (850mg/day). In view of the the low(-ish) calcium and very low magnesium content of the standard Western diets, it does hence appear likely that we would see an even more pronounced increase in serum phosphorus levels and corresponding drop in vitamin D in the "average" American or European convenience food junkie.

In a subsequent paper published in the J. Clin. Invest. three years later Portale, Harris and Curtis revisited the topic and found that (Portale. 1989)

[w]hen these data are combined with those of our prior study [...] the relationship between serum levels of 1,25(OH)2D and 24-h mean serum levels of phosphorus is even stronger (r = -0.90, P < 0.001)"

According to these results, each 1 mg/dL increase in 24h phosphorus levels in your blood, will lead to a subsequent decrease in natural vitamin D by -19 pg/dL - even if all potential confounding variables remain constant (calcium intake, magnesium intake, dietary vitamin D, sun exposure, etc.)


Further evidence: Transient hyperphosphatemia with "normal-high" phosphorus intake

Figure 2: Effect of changes in dietary phosphorus within the normal range on the circadian rhythm in serum phosphorus concentration in normal men. After 8 days of high-normal (2,300 mg/d)or low-normal (625 mg/d) phosphorus intake (Portale. 1989).

What is makes things even more complicated, though, is that the phosphorus overload would probably remain undetected. This is a result of the circadian rhythmicity of serum phosphorus levels. As you can see in figure 2, the "fasted" or at least early morning blood test your local MD usually does will not detect the phosphorus overload, because even in the high phosphorus group serum phosphorus levels are "normal" (2.4 - 4.1 mg/dL) in the morning, but peak at 150% of the normal range in the early afternoon (cf.  figure 2 after the 2nd meal of the day at 12:30pm).

With respect to the underlying mechanism that could be responsible for this interaction between dietary phosphorus intake, serum phosphorus and calcitriol into its active form, Portale et al., speculate that (Portale. 1989)...

"the changes in extracellular concentration of phosphorus might effect changes in the activity of renal 1-hydroxylase" 

And guess what, 1-hydroxylase, which is also known as 25-Hydroxyvitamin D3 1-alpha-hydroxylase, does? Right! It is the enzyme that catalyzes the hydroxylation of the inactive to the active form of vitamin D and thus effectively controls your the concentration of 1,25(OH)2D3 (calcitrol) in your blood.

Question: Do low vitamin D levels protect against hyperphosphatemia?

Against that background it is at least thinkable that our bodies could lower the conversion of vitamin D3 (from skin or diet) into 25OHD, the "storage form" of D3, which is usually measured in blood tests and serves as a precursor to 1,25OHD, to minimize the absorption of dietary phosphorus to 60% (with normal to high levels, it would be >80%; cf. Hollick. 2007) and resort to the exuberant calcium stores in our bones to satisfy their calcium needs. After all, the potential increase in calcium absorption of higher calcitriol levels would be paid for dearly with an even higher influx of dietary phosphorus from the digestive tract and the potential of further leeching of calcium from the bones to reestablish the calcium to phosphorus ratio (Voet. 2004).

Eating no phosphorus at all is not a solution and probably not even necessary

If we now take into consideration that the reduction of phosphorus from a high-normal level of 1,300mg/day (which is identical to the intake of the avg. American in the year 1999-2000; cf.  Ervin. 2004), to 500mg/day did elicit a rapid and almost too pronounced increase to the top (and temporarily even beyond) the normal range, it stands to reason that even a reduction that would yield a ~1:1 calcium to phosphorus ratio, in other words, a phosphorus intake of roughly 900mg/day (identical to the US RDA), could help bring the vitamin D levels back up naturally.

Whether the combination of a low(er) dietary phosphorus load, adequate magnesium and potassium (another phosphorus antagonist intake that has become scarce in the typical Western diet), a reasonable amount of sun exposure and dietary vitamin D from whole foods, alone, will suffice to bring everyone's public vitamin D levels back up, and whether we do even want those levels to be in the >50pg/dL range, which is currently heralded as the lower end of the "optimal range" for serum vitamin D levels, does still have to be elucidated, though.... I must admit, even I have my doubts ;-)

References:

• Ervin RB, Wang CY, Wright JD, Kennedy-Stephenson J. Dietary intake of selected
  minerals for the United States population: 1999-2000. Adv Data. 2004 Apr
  27;(341):1-5. PubMed PMID: 15114720.
• Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. Review. PubMed PMID: 17634462.
• Portale AA, Halloran BP, Murphy MM, Morris RC Jr. Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans. J Clin Invest. 1986 Jan;77(1):7-12. PubMed PMID: 3753709; PubMed Central PMCID: PMC423300.
• Portale AA, Halloran BP, Morris RC Jr. Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men. J Clin Invest. 1989 May;83(5):1494-9. PubMed PMID: 2708521; PubMed Central PMCID: PMC303852.
• Voet, Donald; Voet, Judith G. (2004). Biochemistry. Volume one. Biomolecules, mechanisms of enzyme action, and metabolism, 3rd edition, pp. 663–664. New York: John Wiley & Sons.