Vegetarian nutrient shortcomings

[Guest guest]

Hi All,

Another nutrient that may be deficient in a vegetarian diet is

taurine. This below pdf-available paper, though, also addresses long-

chain fatty acids. " Carninutrients " is a new word to me.

Phytonutrients sounds more natural.

Still, MetaMetrix analysis of amino acids showed low taurine levels

in fish-eating me and they recommended supplementing with taurine.

Eggs have none and milk has little.

Medical Hypotheses

Articles in Press

Sub-optimal taurine status may promote platelet

hyperaggregability in vegetarians

Mark F. McCarty

Summary Although vegan diets typically have a very favorable

effect on a range

of vascular risk factors, several

independent groups have reported that the platelets of vegetarians

are more

sensitive to pro-aggregatory agonists than

are those of omnivores. In light of clear and convincing evidence

that platelet

function has an important impact on risk

for thromboembolic events, it is important to clarify the basis of

platelet

hyperaggregability in vegetarians. A dietary

deficit of long-chain x-3 fatty acids is not likely to explain this

phenomenon,

since most omnivore diets do not include

enough of these fats to discernibly influence platelet function. A

more plausible

possibility is that relatively poor

taurine status – a function of the facts that plants are devoid of

taurine and the

human capacity for taurine synthesis is

limited – is responsible. Plasma taurine levels are lower, and

urinary taurine

excretion is substantially lower, in

vegetarians than in omnivores. Platelets are rich in taurine, which

functions

physiologically to dampen the calcium

influx evoked by aggregating agonists – thereby down-regulating

platelet

aggregation. Supplemental intakes of taurine

as low as 400 mg daily have been reported to markedly decrease the

sensitivity of

platelets to aggregating agonists

ex vivo. Although the average daily intake of taurine from omnivore

diets may be

only about 150 mg, it is credible to

speculate that a supplemental intake of this magnitude could

normalize the

platelet function of vegetarians in the long

term; in any case, this thesis is readily testable clinically.

Taurine is just one

of a number of nutrients found almost

solely in animal products – " carninutrients " – which are rational

candidates for

supplementation in vegans.

Hyperaggregability of platelets

in vegetarians

Low-fat, whole-food vegan diets appear to be of

particular benefit to vascular health, owing largely

to favorable effects on LDL cholesterol, insulin

sensitivity, blood pressure, and body weight [1–7].

However, it is well-known that vegan diets are

devoid of vitamin B12, and homocysteine levels

thus tend to be elevated in vegans who don't sup-plement

with this nutrient [8–11]. Not so well-known

– or understood – is the fact that three

independent research groups have reported that ex

vivo platelet aggregation (using standard agonists

such as collagen, ADP, and epinephrine) tends to

be increased in vegetarians/vegans in comparison

to omnivores [8,12,13]. In light of the fact that

platelet aggregability has been shown to be an in-dependent

risk factor for mortality from coronary

disease [14] – as well as the well-documented

utility of low-dose aspirin and other platelet-sta-bilizing

drugs for preventing heart attack, stroke,

and pulmonary embolism [15–18] – an increase in

the platelet aggregability of vegans might be ex-pected

to have a significant countervailing impact

on the vascular protection afforded by such diets.

Mezzano et al. [9] have suggested that the ab-sence

of long-chain x-3 fats in vegan diets – the

EPA and DHA found in fish oil – may be responsible

for the platelet hyperaggregability observed in

vegans; indeed, they demonstrate that a daily

supplement providing 1400 mg of these fatty acids

can down-regulate ex vivo platelet aggregation in

vegans. However, it is very questionable whether

the omnivore controls in the studies documenting

platelet hyperaggregability in vegans had a suffi-cient

intake of long-chain x-3s to influence their

platelet aggregation. Thus, in the Nurses' Health

Study, the estimated average long-chain x-3 con-sumption

in the top quintile of x-3 intake was es-timated

as only 500 mg daily [19]. Similarly, in the

US Physician's Health Study, subjects in the first

three quartiles of x-3 intake ingested less than 7.4

g long-chain x-3 per month, which amounts to less

than 250 mg daily [20]. Other studies suggest that

the average daily US intake of these fatty acids is in

the range of 100–200 mg [21] There is no prece-dent

for such low intakes of x-3 having a discern-ible

impact on platelet function (And, not

surprisingly, fish consumption had no evident im-pact

on risk for myocardial infraction in the US

Physicians' Health Study.) [22]. In one of the

studies demonstrating platelet hyperaggregability

in vegetarians, the fraction of EPA/DHA in platelet

phospholipids was measured; EPA-which appears to

mediate the benefit of fish oil on platelet function-was

present as only 0.4% of fatty acids in the om-nivores,

as opposed to 0.2% in the vegetarians (by

comparison, arachidonic acid content was around

24% in both groups) [13]. It is hard to believe that

such a low content of EPA could provide meaningful

functional antagonism to the high arachidonate

content of these platelets. Moreover, I am unaware

of any controlled clinical studies in which sub-gram

daily intakes of fish oil x-3s have had a discernible

impact on platelet function. It is instructive to note

that among Greenland Eskimos following their

traditional diets-in whom the platelet-stabilizing

effect of long-chain x-3s was first characterized

[23] – x-3 intake can average 10 g daily [24].

Several studies have attempted to influence

platelet aggregability in vegetarians by adminis-tering

either a-linolenic acid or unicellularly pro-duced

DHA. In one of these studies, ALA (13.5 g

daily) raised the fraction of EPA in platelet phos-pholipids

from 0.2% to 0.5% [25]; in the other

study, in which vegetarians received 1.6 g DHA

daily, the fraction of EPA in platelet phospholipids

rose from 0.21% to 0.58% [26]. In neither instance

was platelet aggregability influenced. In light of

the fact that the platelet EPA fraction of omnivores

in the study cited above was only 0.4%, it is very

difficult to see how better EPA status could ac-count

for the relative hypoaggregability of omni-vore

platelets.

Sub-optimal taurine status as the culprit

I wish to propose the alternative possibility that

sub-optimal taurine status is primarily responsible

for the increased aggregability of platelets in veg-etarians.

Taurine is not found in plant products,

and is present in only minimal amounts in cow's

milk (about 6 mg per cup) [27]. In contrast, all flesh

foods are relatively rich in this nutrient; 100 g of

dark meat from chicken or turkey provides about

200 and 300 mg of taurine, respectively, and

shellfish are an even richer source (over 800 mg in

100 g of scallops, for example). Laidlaw et al. [27]

have estimated the taurine contents of typical

American diets,and found that the daily taurine

intake of omnivores averaged about 150 mg,

whereas lacto-ovo-vegetarians got about 17 mg

daily and vegans got none Japanese researchers

have reported daily taurine intakes in excess of 1 g

in some individuals who made heavy use of sea-food,

and the average daily urinary output of tau-rine

is about 400 mg in certain regions of Japan

[28]. Since taurine is physiologically essential, it is

not surprising to learn that humans do have a

modest capacity to synthesize taurine de novo

from sulfhydryl amino acids [29]. Since the ma-jority

of taurine in humans is eventually excreted

intact in the urine, it is possible to assess the ex-tent

of this synthesis by measuring the 24-h urinary

taurine output of vegans. Laidlaw et al. [30] found

this to be about 33 mg – as contrasted to 113 mg in

omnivores, with an output as high as 250 mg in one

omnivore subject. Evidently, despite some mea-sure

of endogenous synthesis, taurine availability is

much greater in omnivores than in vegans [30,31] –

as reflected in the fact that plasma taurine levels

were found to be 22% lower in vegans than in om-nivores

[30]. The endogenous synthesis of taurine

in vegans presumably is not aided by the fact that

most vegan diets are relatively low in protein and

thus sulfhydryl amino acids, which provide the

sulfur required for taurine production. Fortunately,

up-regulated renal retention of taurine enables

vegans to maintain plasma taurine levels that are

not grossly subnormal [32].

One of the physiological functions of taurine is

to modulate platelet aggregation. Platelets avidly

concentrate taurine, and, for reasons not yet clear,

this taurine tends to blunt the calcium influx trig-gered

by pro-aggregant agonists, thereby rendering

platelets more stable [33]. When cats, which lack

the ability to synthesize their own taurine, are

placed on a taurine-free diet, the aggregability of

their platelets doubles [34]. Type 1 diabetics have

been reported to have relatively low plasma tau-rine

levels – about 30% lower than in omnivores,

not dissimilar to the situation in vegans – and this

is associated with increased platelet aggregability

[35]. Conversely, taurine supplementation – in

healthy male subjects (presumably omnivore), type

1 diabetics, and cats – has been shown to decrease

platelet aggregability [34,35]. In one of these

studies, the platelet aggregation threshold for

collagen rose by over 40% in healthy subjects re-ceiving

400 mg taurine for 14 days [34]. Plasma

taurine rose by about 50% during this time, and the

rise in platelet taurine was slightly greater than

this. No comparable studies in vegans have been

reported.

Admittedly, 400 mg is greater than the 150 mg or

so provided by average American omnivore diets.

But it is notable that the response of platelets to

the 400 mg dose was quite large and was still rising

when the study terminated after 14 days. Fur-thermore,

given the fact that the platelets of ve-gans

can be presumed to be relatively taurine

deficient, is seems likely that their platelets would

be more responsive to a modest supplemental in-take

of taurine than the platelets of omnivores

would be. So it is reasonable to suspect, based on

the data cited above, that administering 150 mg of

taurine daily to vegetarians on a continuing basis

would have a significantly beneficial impact on

their platelet hyperaggregability, and quite possi-bly

would eliminate the disparity between vege-tarians

and omnivores in regard to platelet

function. This prediction is readily clinically test-able.

In the study of Li et al. [13], comparing platelet

aggregation in omnivores, ovo-lacto-vegetarians,

and vegans, the authors segregated the omnivores

into " high meat eaters " and " moderate meat eat-ers " .

Notably, they found that platelet aggrega-bility

was consistently lower (albeit not to a

statistically significant degree) in the high meat

eaters than in the moderate meat eaters; platelet

aggregability did not differ between the ovo-lacto-vegetarians

and vegans, in whom it was signifi-cantly

higher than in either group of omnivores.

Since flesh foods are the chief dietary source of

taurine – whereas dairy products have only mini-mal

levels – these findings track nicely with the

taurine contents of the various diets. In other

words, platelet aggregabilty may vary continuously

as a function of the taurine content of ordinary

diets.

In light of the clear impact of platelet function

on vascular risk, establishing that supplemental

taurine can normalize platelet aggregation in veg-etarians

could be of great practical importance.

Fortunately, taurine is inexpensive and has no

known toxicity, even in high doses. Thus, it would

be quite feasible for vegetarians to supplement

their diets with taurine in doses comparable to or

greater than those found in high-flesh diets. It is

pertinent to note that the ability of taurine to

down-regulate platelet aggregation is comple-mentary

to that of aspirin [36]; thus, taurine could

be useful to subjects who are already using low-dose

aspirin to decrease their risk for thrombo-embolic

events. Moreover, in ample, multi-gram

daily doses, taurine appears to have antihyper-tensive

activity [28,37,38], and has been shown to

have a safe positive inotropic effect in congestive

heart failure [39–41]. Furthermore, supplemental

taurine has shown antiatherogenic activity in ro-dent

models of hypercholesterolemia, even when

taurine fails to influence serum lipid levels

[42–44]. This latter finding is of particular interest

in light of recent epidemiology suggesting that in-creased

expression of myeloperoxidase may pro-mote

coronary atherogenesis in humans [45,46];

taurine is the natural antagonist of hypochlorous

acid, the chief oxidant produced by myeloperoxi-dase

[47,48]. Finally, anecdotal Italian clinical

reports dating back over 3 decades suggest that

high-dose taurine may provide marked symptom-atic

benefit in angina and intermittent claudica-tion,

for reasons that remain obscure [49]. Thus,

taurine supplementation as a strategy for promot-ing

vascular health deserves much further atten-tion

than it so far has received – and it stands to

reason that vegetarians, with poor baseline taurine

status, would benefit the most from such supple-mentation.

Some vegans might contend that, in light of the

minimal risk for coronary disease enjoyed by quasi-vegan

Third World societies, taurine supplemen-tation

of vegan diets represents an exercise in

" gilding the lily " . But this view ignores the fact

that vegans do not enjoy privileged status with

respect to risk for stroke – indeed, age-adjusted

stroke mortality is quite high in many rural Asian

cultures whose quasi-vegan diets provide effective

protection from coronary disease [50,51]. Fur-thermore,

a good many Western subjects adopt

this diet for health reasons after they have already

developed some degree of coronary disease. Al-though

therapeutic regimens stressing low-fat,

whole-food vegan diets have a very favorable im-pact

on the subsequent clinical course of such in-dividuals,

they do not provide complete protection

from coronary events [52]. Thus, the inclusion of

nutritional or pharmaceutical adjuvants in such

protocols is entirely appropriate.

" Carninutrients " for vegetarians

My conclusion that deficiency of long-chain x-3 fatty

acids is not at the root of the hyperaggregability of

platelets in vegetarians, is in no way intended to

denigrate the utility of x-3 supplementation – in

vegetarians as well as omnivores – for health pro-motion

[53,54]. The practical difficulty for vege-tarians

in this regard is that most vegetarians choose

this diet for ethical reasons, and would prefer not to

use fish oil. Administration of a-linolenic acid to

humans, even in high doses, typically fails to repli-cate

the health benefits conferred by relatively

modest intakes of fish oil, most likely because hu-man

d-6-desaturase activity is low [25,55,56]. Uni-cellular

DHA is now available, but is expensive and

does not confer the full range of benefits of fish oil,

since retroconversion to EPA is not very efficient

[26]. A practical way to solve this dilemma would be

to alter flaxseed genetically such that it expresses

high d-6-desaturase activity; flax would then pre-sumably

convert a significant proportion of its a-li-nolenic

acid to stearidonic acid (18:4n3), which

humans, in turn, should readily convert to EPA and

DHA. This strategy might provide a quite inexpen-sive

and virtually inexhaustible terrestrial source of

x-3 that would be no less health protective than fish

oil – and that would be acceptable to ethical veg-etarians.

Taurine is one of several nutrients found pri-marily

in animal products – long-chain x-3, carni-tine,

creatine, carnosine, and of course vitamin

B12, come readily to mind – that have health-protective

potential. I propose that these sub-stances

be designated " carninutrients " , so that

they will receive the respect and attention cur-rently

accorded to phytonutrients (nutrients and

food factors found solely in plants). To qualify as a

carninutrient, a nutrient should: (1) be present in

flesh foods to such an extent that omnivores can

and usually do obtain physiologically meaningful

amounts from flesh foods; (2) Either is not present

in plant foods, or is present in such limited quan-tities,

or so sporadically, that most vegans get

amounts that are physiologically trivial (e.g., car-nitine)

or markedly suboptimal for health (e.g.,

vitamin B12). Note that a nutrient that is not lit-

erally absent from all plant foods can still qualify as

a carninutrient; thus, EPA/DHA can be obtained

from seaweed, vitamin B12 from plant foods con-taminated

with bacteria or insect parts, and car-nitine,

in tiny amounts, in avocados – yet these

nutrients can reasonably be considered carninutri-ents,

as most vegans get minimal amounts from

unsupplemented diets.

It would be feasible and appropriate for vege-tarians

to supplement with carninutrients in

amounts comparable to or greater than those

supplied by omnivore diets. The health benefits

likely conferred by ample intakes of long-chain x-3

fats are versatile and impressive [53,54]; in par-ticular,

the ability of these fats to stabilize plate-lets

in vegans has been documented [9]. The

creatine present in cooked meats can give rise to

heterocyclic amine mutagens likely to contribute

to the burden of human cancer [57], but this nu-trient

seems to be innocuous when consumed as a

dietary supplement [58]. The muscle creatine pool

tends to be lower in vegetarians than in omnivores,

and supplemental creatine has a greater impact on

this pool in vegetarians [59]. Although supplemen-tal

creatine is currently used primarily for the

somewhat frivolous purpose of making strong

people a bit stronger [60], evidence from rodent

studies suggests that high intakes of creatine may

have valuable neuroprotective activity [61,62];

whether high-dose creatine might benefit certain

aspects of cardiac metabolism merits further study

[63]. Although a severe degree of vitamin B12 de-ficiency

occasionally leads to a syndrome reminis-cent

of pernicious anemia in vegans [64,65], it is

more common for a less severe deficit of this vi-tamin

to elevate homocysteine levels in vegetari-ans/

vegans [8–11].

Vegan diets contain virtually no carnitine, and

plasma carnitine levels tend to be low in vegans, in

part because their diets are also relatively low in

the biosynthetic precursors of this agent, lysine

and methionine [66–68]. However, it is not clear

whether the low-normal carnitine status of vegans

has significant functional consequences. Supple-mental

carnitine can improve the bioenergetics of

ischemic cardiac or skeletal muscle [69–74], and

thus may be particularly appropriate when patients

with cardiac ischemia or intermittent claudication

adopt a vegan diet. Supplemental carnitine may

also promote control of plasma triglycerides in

some subjects [74], but this application has only

been studied adequately in hemodialysis patients.

Carnosine is a dipeptide with antioxidant and che-lating

activity present in millimolar concentrations

in muscle and neurons [75]. Whether the camosine

content of omnivore diets provides any health

benefit is currently unclear, nor is it known whe-ther

the tissue carnosine pool is lower in vegans

than in omnivores.

Although selenium does not formally qualify as a

carninutrient, vegans should be aware that they

are at increased risk for poor selenium status

(relative to omnivores) if they live in an area where

soil selenium levels are low, such as many regions

in Europe [76–78]; low intakes of selenium may

increase risk for vascular disease [79], whereas

relatively high intakes may reduce cancer risk

[80–82]. Vegans, who by definition do not use dairy

products, seem to have relatively good bone health

despite low calcium intakes [83,84] – but supple-mental

calcium would likely provide further benefit

in this respect. Moreover, recent evidence suggests

that good calcium nutrition may reduce risk for

obesity, insulin resistance, and colon cancer

[85–87] Good vitamin D status is also clearly ben-eficial

for bone health [88,89], and there is some

reason to suspect that it may also complement the

benefits of calcium in reducing risk for insulin re-sistance

and obesity, while in addition aiding pre-vention

of hypertension and certain common forms

of cancer and autoimmune disease [90–95]. En-riched

dairy products are apt to be the chief die-tary

source of vitamin D for omnivores and lacto-ovo-

vegetarians (albeit omnivores can also get

significant vitamin D nutrition from liver and oily

fish); aside from rather trivial amounts of vitamin

D2 found in mushrooms and seaweed, vegan diets

are essentially devoid of this vitamin. Vegans living

at northern latitudes are likely to experience poor

vitamin D status during winter months if they do

not supplement with adequate doses of vitamin D

[96–98].

Clearly, while vegetarian and especially vegan

diets are highly commendable from the standpoint

of their long-term health impacts, they – like any

other natural diet-have a few " Achilles heels " that

can be addressed effectively with rationally plan-ned

nutritional supplementation.

Cheers, Alan Pater