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Soy protein - yea, or nay?

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It has come to this - I would like to find a decent protein powder. I'm thinking of giving up fish, and so the only requirement I have is that the protein powder be non-animal in origin, so no whey etc.


I keep looking at pea protein, but my preferred source truenutrition.com has a pea protein that I find very difficult to handle - basically I find it impossible to dissolve, and this is an important criterion for me (plus it has high levels of sodium). Other vegan options are not attractive for a variety of reasons (hemp, rice, pumpkin etc.). Their Soy Protein Isolate looks great with regard to methionine, cystine, leucine etc. not too high, good calorie/protein ratio and so on. However, a giant - did I say GIANT - caveat, is the dementia danger, per the famous and well-designed Lon White study.


I know Dean is somewhat skeptical of the dementia connection what with lack of followup studies (I don't believe it to be a valid argument in and of itself - if the study is well-designed, its conclusions are not obviated by lack of further studies). However, what I wonder is if there is any meaningful distinction to be made between tofu (which is what the Lon White study focused on) and soy protein isolate.


So my question is, for anyone who wants to chime in: how safe would it be to regularly consume soy protein isolate? 


I performed a search in the forums here, but can't guarantee that I caught all of the threads dealing with soy protein, though here's one of Dean's posts.


I also scoured PubMed for papers using search terms such as "soy protein brain", and found one interesting study, which I got full text access to thanks to sci-hub, and I show it below. 


Unfortunately there are still not many studies that deal with humans, most of the searches came back with rodents, which is drastically less useful. However, I have included a bunch of studies that deal glancingly with brain or neural health and soy. Obviously, these are not as good as a Lon White study with soy protein instead of tofu would be, but here we are. While searching for studies, I've of course come across many that were not relevant to the subject at hand, but interesting in their own right (and a couple of studies which might be of special interest to Dean, especially that one deals with BAT and another with core body temperature :)... anyhow, I've gone ahead and posted them here just for general interest.


Of the greatest interest is PMID: 21035431 “Borobudur revisited: soy consumption may be associated with better recall in younger, but not in older, rural Indonesian elderly.”


With full text thanks to sci-hub:



The picture that emerges from this study is rather mixed. It does appear that intake of high levels of isoflavones is associated with memory and dementia effects, but it is by no means a linear effect as found by Lon White et al. A distinction is made between tofu and tempeh, the consumption of which were both measured. Tempeh and tofu have different phytochemical profiles, f.ex. tempeh, which is fermented, having a particularly high genistein and generally higher levels of isoflavones compared to tofu.


Tofu and tempeh consumption appears to have different effects in the study population, but the most significant factor was the fairly pronounced difference between those consumers who were younger than 66 years (where the consumption appeared to have a beneficial effect at least on word recall) and older, where there were some negative effects. Those negative effects however did not appear very strong and after adjustments for education and other factors were hovering around significance. It also appears that folate found in some of these products might be protective against any negative effects, and independently possibly even fruit consumption might be helpful.


The other value of this study were the references for other studies that examined the tofu/tempeh/dementia connection.


My biggest takeaway was the apparent differences between the various soy products, and even possibly adulterants in some of them (formaldehyde etc.) and their effects on brain health. In this context it seems therefore to me that one can’t simply take tofu or tempeh and extrapolate from that to brain effects that might, or might not result from the consumption of soy protein isolate.


What one needs are studies of soy protein isolate specifically and brain health - for understandable reasons, these are not likely to be many such longitudinal studies in humans.


An overview of phytoestrogens and health:


The pros and cons of phytoestrogens.    


A search of PubMed for soy protein and brain resulted in such studies only glancingly related, but at least in humans. Of tenuous relevance to my situation:


Attenuation of neurodegeneration-relevant modifications of brain proteins by dietary soy.


Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function.




Preventive Effect of Soybean on Brain Aging and Amyloid-β Accumulation: Comprehensive Analysis of Brain Gene Expression.


Unfortunately focused just on soy peptides, and narrow mechanistic effects, but at least not negative (and again, in humans):


Effects of soybean peptide on immune function, brain function, and neurochemistry in healthy volunteers.


And more mechanistic stuff, but at least in humans:


Protective effects of genistein on proinflammatory pathways in human brain microvascular endothelial cells.


The soy isoflavone, genistein, protects human cortical neuronal cells from oxidative stress.


But maybe beware of high levels of consumption of genistein (rat study):


Evidence for genistein mediated cytotoxicity and apoptosis in rat brain.


Maybe it’s the dose that makes the poison (alas, in vitro):


Genistein ameliorates beta-amyloid peptide (25-35)-induced hippocampal neuronal apoptosis.



Perhaps interesting to Dean (effect on BAT) - but in rats:


Dietary isoflavones alter regulatory behaviors, metabolic hormones and neuroendocrine function in Long-Evans male rats.


Also for Dean, though irrelevant to the subject at hand:


Long-term high-soybean oil feeding alters regulation of body temperature in rats.


Search for nutritional confounding factors in the relationship between iron deficiency and brain function.


[Vitamin K in the Norwegian diet and osteoporosis].




Which characteristic of Natto: appearance, odor, or taste most affects preference for Natto.


I hope Dean also finds interesting the following study on Long Term Moderate CR and aging - though again, rats. Soy protein didn’t seem to add much of anything to the benefits of Long Term Moderate Calorie Restriction gene expression in the rat anterior pituitary and hypothalamic tissues, but importantly - seems to me - it didn’t seem to do any harm either.


Aging and diets regulate the rat anterior pituitary and hypothalamic transcriptome.


This doesn’t sound good and the study was done in monkeys:


Increased aggressive behavior and decreased affiliative behavior in adult male monkeys after long-term consumption of diets rich in soy protein and isoflavones.


And this one in mice, but likely completely irrelevant:


Soy-based diet exacerbates seizures in mouse models of neurological disease.


Rodents and more rodents. I wish this was in humans, rats! For what it’s worth:


PMID: 1686810

Effect of amino acid supplementation to a low-protein diet on brain neurotransmitters and memory-learning ability of rats.


PMID: 24678753

Oral administration of soy peptides suppresses cognitive decline by induction of neurotrophic factors in SAMP8 mice.


PMID: 24450802

Soyasaponins Ab and Bb prevent scopolamine-induced memory impairment in mice without the inhibition of acetylcholinesterase.


PMID: 23948892 

Early intervention with an estrogen receptor β-selective phytoestrogenic formulation prolongs survival, improves spatial recognition memory, and slows progression of amyloid pathology in a female mouse model of Alzheimer's disease.


PMID: 23766238

Soybean isoflavone ameliorates β-amyloid 1-42-induced learning and memory deficit in rats by protecting synaptic structure and function.


PMID: 23469956

Soy isoflavone alleviates Aβ1-42-induced impairment of learning and memory ability through the regulation of RAGE/LRP-1 in neuronal and vascular tissue.


PMID: 23239252

Soy isoflavone attenuates brain mitochondrial oxidative stress induced by β-amyloid peptides 1-42 injection in lateral cerebral ventricle.


PMID: 17289196 

Memory performance of hypercholesterolemic mice in response to treatment with soy isoflavones.


PMID: 19132270

Effects of soy milk as a dietary complement during the natural aging process.


PMID: 22736505

Genistein induces growth arrest and suppresses telomerase activity in brain tumor cells.


PMID: 22551092

Antagonizing effects of soybean isoflavones on β-amyloid peptide-induced oxidative damage in neuron mitochondria of rats.


PMID: 20954807

Soybean supplementation helps reverse age- and scopolamine-induced memory deficits in mice.


PMID: 19146912

Soy isoflavones attenuate oxidative stress and improve parameters related to aging and Alzheimer's disease in C57BL/6J mice treated with D-galactose.


PMID: 15226476

Soy isoflavones improve spatial delayed matching-to-place performance and reduce cholinergic neuron loss in elderly male rats.


PMID: 12727319

Stress (hypothalamic-pituitary-adrenal axis) and pain response in male rats exposed lifelong to high vs. low phytoestrogen diets.


Highly interesting sex-based differential outcome - free full text (but again, rats):


Visual spatial memory is enhanced in female rats (but inhibited in males) by dietary soy phytoestrogens.

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Wow Tom,


That's quite a list of references - several of which were indeed quite interesting for me. Thanks!


Regarding soy protein. I'm not a fan of protein isolates anymore, since we figured out excess protein seems to be anti-CR. Can't you get the RDA of protein from whole food sources Tom, even without the fish?


As I said in that post you pointed to, when I did use protein isolates, including soy (and pea and hemp), I used this low-isoflavone "Essential" soy protein from MotherSoy, to avoid getting too many phytoestrogens. As you've seen, the effects of phytoestrogens are a morass - hard to know what they're gonna do to you long term. Could be very good, or pretty bad. Depends on whether you are male or female, human or rodent. I just decided to stay away, except for the few grams of soybeans I get from natto daily.


BTW, here was the Kirkman pea protein isolate I used to eat as well, in case that piques your interest as an alternative or adjunct to soy. 



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Thanks, Dean, for those links. I looked at the Essential soy protein from MotherSoy, and while I liked very much the fiber content, I could not find any support for the claim that it's low isoflavone - the only claim re: isoflavone I found was one for Essential Isoflavone variety that has DOUBLE the amount of isoflavone. Did I miss it somehow?


Well, I don't wish to consume excess protein, that's for sure. However, I do have an interest in controlling the amino-acid profile of my protein, which is why I turn to protein powder, as at least on truenutrition site, you can order your own blend. Unfortunately, their bulk powders profiles are whatever the source is. In any case, I'm interested in low methionine, cysteine, leucine etc., vegetarian protein. 

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Regarding mothersoy soy protein - you may be right. I've always thought that at 8mg isoflavones per 25g serving, their "Essential" soy was reduce in soy relative to other soy protein powders, but perhaps that was only relative to their other, higher-isoflavone product, and not soy protein isolates in general.

 In any case, I'm interested in low methionine, cysteine, leucine etc., vegetarian protein.


Again I wonder - why not just eat the whole vegetables, which themselves are low in total protein, methionine, and BCAAs.




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Well, that goes to the whole workflow and efficiency question. It's also bang for the calorie buck. Concentrated protein is... concentrated protein - the most efficient way of getting your amino acids for the least amount of calories, and hassle factor. Ultimately, to optimize a diet, one has to personalize it to one's own particular profile of vulnerabilities and strengths. I have persistent trouble with my elevated LDL (124-132 mg/dL) that with my naturally high HDL (though thankfully low trigs) translates into high TC (200 - 210 mg/dL). So I am always concerned about my CV health - that is my particular risk profile around which I build my diet. I also happen to have alleles that predispose me NOT to benefit from F&V when it comes to CV health (alleles that you Dean also share). But unlike Dean, my LDL and consequently TC is in the pits, and I must always take measures. To get protein by piling on more F&V (of which I already eat a fair amount for other reasons) is not going to translate into CV benefits, so I have no incentive to look for my protein from whole foods in the F&V department. And the most efficient way to get my protein would be from a vegetable-source concentrated protein - at the lowest calorie cost, not having to eat a lot more F&V (I am concerned about my teeth wearing - cautioned by my dentist - as I consume quite a bit of F&V, nuts and the like already). I also do not want the sheer volume of food I'd have to consume compared to a concentrated protein. And concentrated protein is easier to source and store - unlike F&V where you have to constantly shop for and then refrigerate at great volume.


I eat twice a day. For my breakfast I am now developing a "soup" recipe (I like to combine!) that would incorporate a protein powder. I have done a fair amount of research into psyllium, and I intend to incorporate two tablespoons of psyllium in two forms into the soup, plus tablespoon of nutritional brewer's yeast, tablespoon of ground flaxseeds, tablespoon of oat bran/starch and the VEGETABLE PROTEIN POWDER - X, which I'm trying to identify. I then want to mix all those powders and dissolve them in green tea for consumption with my breakfast.


Bottom line: it's about diet composition and workflow.

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I understand Tom. Makes sense.


BTW, in researching this post I stumbled across readily available information that shows soy milk has about 30 mg of isoflavones per 1-cup (8oz) serving. This is about 4x the amount in a 25g serving of MotherSoy Essential Protein isolate. So that protein powder is indeed relatively low when it comes to soy isoflavones.


 I have persistent trouble with my elevated LDL (124-132 mg/dL) that with my naturally high HDL (though thankfully low trigs) translates into high TC (200 - 210 mg/dL). So I am always concerned about my CV health - that is my particular risk profile around which I build my diet. 


Since you're not averse to powders and are already making a breakfast soup/smoothie, have you considered adding some resistant starch (RS) to your mix? This recent study [1] found it was somewhat less effective for blood glucose control, but more effective for lowering cholesterol than traditional sources of fiber. Here is the table of their results, with the important cholesterol rows highlighted:




But that was just an observational study based on food frequency questionnaires, and in obese pre-diabetics - so not too close to our demographic... 


This study [2] is much more relevant since you're considering soy, and it used people like you. It was a controlled crossover design intervention trial involving mildly hypercholesterolemic people who weren't on statins or other medication. They fed them either soy (as soy milk and soy cereal) + a probiotic yogurt or soy + prebiotic resistant starch for five weeks. It found the soy + RS diet was slightly better than the soy + yogurt diet for controlling cholesterol - reducing both total and LDL cholesterol by 5.5% and 7.3% respectively. Interestingly, the soy didn't make any difference for cholesterol.


I personally include a tablespoon of a 33/33/33 blend of potato starchplantain flour and psyllium husk powder in my blended "salad dressing" to thicken it as well as boost the RS/fiber content. These might be worth considering as additional ingredients in your "witch's soup" ☺.





[1]  Eur J Nutr. 2016 Feb;55(1):127-37. doi: 10.1007/s00394-015-0831-3. Epub 2015 Jan 

Effects of total fibre or resistant starch-rich diets within lifestyle
intervention in obese prediabetic adults.
Dodevska MS(1), Sobajic SS(2), Djordjevic PB(3), Dimitrijevic-Sreckovic VS(3),
Spasojevic-Kalimanovska VV(4), Djordjevic BI(2).
PURPOSE: Starting from the evidence-based health benefits that resistant starch
(RS) shows when added to the diet, our aim in this study was to evaluate the
effects of increased fibre intake with two different levels of RS coming from
regular daily consumed foods on normalization of glycaemia within lifestyle
intervention in the population with risk factors for developing diabetes.
METHODS: Study included 47 overweight and obese men and women with disordered
glucoregulation and dyslipidaemia, aged between 45-74, divided into RS and Fibre 
group. Participants were subjected to the lifestyle and dietary intervention with
low-fat and high-fibre (>25 g/day) diet for 12 months and were offered two
different dietary advices aimed at increasing total fibre intake in Fibre group
and at increasing RS intake in RS group.
RESULTS: The intake of macronutrients and total fibre was similar between groups 
at the end of the study, but achieved RS intake was two times higher in the RS
group. Decrease in total cholesterol and non-HDL-cholesterol was more pronounced 
in RS group in comparison with Fibre group (p = 0.010, p = 0.031, respectively), 
whereas in Fibre group, a more pronounced effect on glucoregulation was observed:
significant fall in glycaemia after 2-h oral glucose tolerance test (7.93 vs
6.96 mmol/L, p = 0.034).
CONCLUSION: At the end of the study, RS-rich diet failed to affect glycaemic
control in prediabetic obese individuals in contrast to the regular fibre-rich
diet, which indicated that fibre profile could be an important determinant of the
effect of dietary intervention.
DOI: 10.1007/s00394-015-0831-3 
PMID: 25588971
[2] Eur J Clin Nutr. 2009 Feb;63(2):238-45. Epub 2007 Oct 17.
Dietary combination of soy with a probiotic or prebiotic food significantly
reduces total and LDL cholesterol in mildly hypercholesterolaemic subjects.
Larkin TA(1), Astheimer LB, Price WE.
OBJECTIVE: We hypothesized that a dietary combination of soy with either a
probiotic (yoghurt) or a prebiotic (resistant starch) would result in enhanced
lipid-lowering effects compared with a control soy diet, possibly via
improvements in isoflavone bioavailability.
SUBJECTS: Mildly hypercholesterolaemic subjects (men and post-menopausal women)
older than 45 years were recruited via the local media. Thirty-six subjects
commenced the study; five withdrew.
RESULTS: Soy+probiotic significantly decreased total cholesterol (4.7+/-2.0%;
P=0.038) and soy+prebiotic significantly decreased total and low-density
lipoprotein cholesterol (5.5+/-1.6%; P=0.003 and 7.3+/-2.2%; P=0.005,
respectively). The bioavailabilities of daidzein, genistein or equol were not
affected by probiotic or prebiotic consumption or associated with lipid changes.
CONCLUSION: Dietary combination of soy with either a probiotic or a prebiotic
resulted in significant lipid lowering, not related to isoflavone
DOI: 10.1038/sj.ejcn.1602910 
PMID: 17940545
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Absolutely, Dean, RS is in my crosshairs - along with the super-viscous fiber (there's a paper I found when researching psyllium that found viscosity as the dispositive characteristic in cholesterol control, the more viscous the better control). As you know, Dean, diet is an evolving thing, so I'm always tinkering with it. Thank you for the pointers, and I'm definitely still working on the "witches soup" :)


My wife and I have been making kefir from kefir grains for a few years now. I used to drink a small amount daily (about a cup), but then about a year ago I cut if off on grounds of not adding calories (my wife has continued). In view of the info you've supplied, I may have to re-visit that decision. The nice thing about the kefir-making is that you can make kefir out of almost anything and add almost anything (that will not actually kill the kefir bugs!). 

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I personally include a tablespoon of a 33/33/33 blend of potato starchplantain flour and psyllium husk powder in my blended "salad dressing" to thicken it as well as boost the RS/fiber content. These might be worth considering as additional ingredients in your "witch's soup" ☺.


My witches soup already calls for 1 tablespoon of psyllium husk powder and 1 tablespoon of psyllium whole husks. When you say "boost RS/fiber content", I assume by "fiber" you mean the psyllium part - which as far as I understand it is not RS (resistant starch). However, it is the potato starch and the plantain flour where it gets tricky. First, plantain flour - is this based on the idea that unripe bananas have high levels of RS? Because do we know for sure that plantain flour = unripe banana RS? That's not obvious to me at all.


Furthermore, as you know RS comes in 4 classes RS1 - through RS4. Each is relevant to a different part of the digestive system and exercises its effects through different means. There are also claims - not surprising I suppose - that favoring one and excluding another may be counter-indicated. While looking into this question, I came across this blog entry, but have not had the time to chase down all scientific papers cited in support of the various contentions - it's nonetheless interesting "food for thought":


Don't Take Resistant Starch Alone and Other Precautions; RS2 Needs to Be Taken With Other Fiber To Spread Fermentation Completely Across the Entire Colon


This whole fiber/RS topic is going completely off subject of this thread, but in turn I think deserves its own thread, given the vital importance of fiber, resistant starches and our gut biota - and you of all people, Dean, are a champion of the salutary effects of super-high levels of fiber consumption. I don't know if such a thread already exists, and we should just move this part of the discussion there, or a new thread needs to be created. I do confess that when I saw a whole continent open up in front of me upon reading about RS1, RS2, RS3 and RS4, I was gripped by a feeling of raw panic - I am in no position to now start a massive research project exploring fiber, as I'm already swamped by WBV with HH looming on the horizon - and as happens a couple of weeks ago I completed a few days worth of research into psyllium. We need to clone Dean. In any case, I thought you may want to take another look at your RS/fiber 33/33/33.

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I do confess that when I saw a whole continent open up in front of me upon reading about RS1, RS2, RS3 and RS4, I was gripped by a feeling of raw panic - I am in no position to now start a massive research project exploring fiber...


Sigh... Tom, I'm not sure if you or Michael is the better poster child for the adage "The perfect is the enemy of the good." Or in your case, it seems sometimes like an acute case of "analysis paralysis". 


The whole body vibration hesitancy is once thing. But given your pretty bad cholesterol despite a healthy diet and lifestyle, it would seem to me this is one instance where you might consider putting aside your ultra-conservative & prefectionionist tendencies and try adding some resistant starch to your diet.


Ever think you might experiment to see if it helps you or not? Whatever...


In any case, I thought you may want to take another look at your RS/fiber 33/33/33.


Nope. I go for fiber diversity by combining two forms of resistant starch (potato and unripe plantain) with a form of mostly soluble fiber (psyllium) and leave it at that. Another case of leveraging diversity to cope with uncertainty. Is there still risk associated with my calculated heedlessness? Of course. There is always risk.



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