35th World Vegetarian Congress
'Food for all our futures'
Heriot Watt University, Edinburgh, Scotland
July 8-14, 2002
by Stephen Walsh, PhD
- Chemistry and functions of vitamin B12 and folate
- Classical deficiency: symptoms and timing
- B12, folate and homocysteine in vegetarians
- Homocysteine and mortality
- Observed vegetarian mortality
- Homocysteine and birth defects and other health issues
- Intervention trials with B vitamins
- How much B12 is enough?
- Sources of B12
- B12 and natural diet: where do other primates get their B12?
- Testing for B12
The role of B12 and folate
B12 along with folate is required to convert homocysteine to methionine.
If this conversion is blocked then homocysteine levels rise, driving SAH levels up and blocking vital methylation reactions.
These methylation reactions are required to:
- Stabilise DNA, RNA and proteins
- Produce neuro-transmitters
- Produce Coenzyme Q (antioxidant)
- Eliminate toxins such as pyridine and arsenic
If folate is deficient and DNA synthesis is directly retarded causing enlarged red blood cells (megaloblastic anaemia) and impairing methylation.
If B12 is deficient methylation is impaired and folate is partially trapped (methyl-folate trap) causing megaloblastic anaemia.
B12 deficiency with high folate intake causes nervous system damage rather than anaemia.
Homocysteine is a pro-oxidant and probably directly toxic
Both B12 and folate deficiency prevents sufficient DNA being produced to replenish blood cells resulting in a reduced number of enlarged red blood cells and anemia.
Main symptom is lack of energy.
This is more often associated with B12 deficiency than folate deficiency. Symptoms include:
Numbness and tingling, Lack of energy, Blurred vision, Sore tongue, Loss of balance and limb control, Poor memory, Personality changes including delusions and paranoia.
In infants B12 deficiency manifests as loss of energy, appetite and alertness and can progress to coma and death. Onset is more rapid than in adults.
All symptoms are reversible if caught early enough but damage can be permanent, particularly in children.
NB breastfed infants can become severely deficient if the mother has low B12 intake, even if the mother has no symptoms.
How long does it take for B12 deficiency to develop?
The liver stores about 1500 m g of B12 if blood levels are about 300 pmol/l.
0.1% of this is lost per day by secretions into the gut as not all these secretions are reabsorbed.
As B12 levels drop, the amount secreted into the gut decreases and the fraction reabsorbed increases, slowing the fall in blood B12.
How fast B12 levels change depends on the balance between how much B12 is obtained from the diet, how much is secreted and how much is absorbed.
Genetic variations in enzymes such as MTHFR determine how rapidly homocysteine will rise and when nervous system damage will begin as B12 levels fall.
These variations explain why clinical B12 deficiency may arise in a year if initial stores are low and genetic factors unfavourable or may not appear for decades.
In infants deficiency can appear much more quickly.
Clinical deficiency sometimes occurs at levels below 200 pmol/l but usually occurs below 70 pmol/l.
Homocysteine levels increase as B12 levels fall below 300 pmol/l and rise dramatically below 150 pmol/l.
B12 and folate levels in vegans, vegetarians and meat-eaters
Homocysteine levels in vegans, vegetarians and
Early hopes that moderate vegan protein intake and higher folate intake would lead to lower homocysteine have been shown to be overwhelmed by lower B12 levels.
The homocysteine levels of the Chilean vegetarians above dropped to 7.9 on supplementation with B12.
The good news is that with adequate B12 the advantages of a vegan diet (high folate and moderate protein) come through as shown in the USA, 1999 study.
If typical meat-eaters switch to a well designed vegan diet homocysteine drops.
Homocysteine and Health
|Threshold||times 2.7||plus 5||+14||+14|
Homocysteine levels in healthy people with good levels of B12 and folate are about 8 m mol/l. Average levels are about 10 m mol/l, rising with age.
Average vegan levels are about 14 m mol/l. Based on the above data this excess homocysteine could be associated with a 40% increase in mortality, particularly from heart disease and other causes.
Low vegan cholesterol levels lead to predicted heart disease deaths about 50% those of meat-eaters, so the overall result would be expected to be 30% less heart disease, but 40% increased mortality from other causes, with little difference overall.
Observed vegetarian mortality
(UK, USA and Germany, 1999)
|Relative risk of death
(95% confidence interval)
|Regular meat-eaters||Occasional meat-eaters||Fish-eaters||Vegetarians||Vegans|
|Other causes||1.00|| 0.84
|All causes||1.00|| 0.84
- Vegan heart disease mortality: 0.74 vs 0.7 predicted
- Vegan other cause mortality: 1.33 vs 1.4 predicted
- Overall outcome: lacto-vegetarians, fish-eaters and occasional meat-eaters can expect to live about two years longer than vegans.
- Top candidate for reason: elevated homocysteine.
- The opportunity: adequate B12 could put vegans ahead of everyone else.
|Neural tube defects, B12 and
|B12||<180 pmol/l||180-280 pmol/l||>280 pmol/l|
|Homocysteine, birth defects and
complications (Norway, 2000)
Comparing 25% with highest homocysteine with 25% with lowest homocysteine:
|Low birth weight||2.01|
|Neural tube defects||3.57|
Homocysteine above 15 m mol/l was also associated with 3 times the risk of placental abruption (miscarriage).
Other health issues
There is a strong association between elevated homocysteine and dementia (both vascular dementia and Alzheimer?s disease) and with cognitive decline.
The most recent UK studies on vegetarians (UK, 2002) found higher mortality from neurological and mental disease in vegetarians than in nonvegetarians, though overall mortality was almost identical.
Elevated homocysteine is also associated with depression.
Intervention trials with B vitamins
Neural tube defects
4 mg of folic acid reduced neural tube defects by 72% (MRC, 1991)
0.8 mg of folic acid and 4 m g of B12 reduced neural tube defects by 100% (Czeizel, 1992)
Two trials with folic acid, B12 and B6 have shown reductions in the development of atherosclerosis.
One, which had no control group, and may have a strong bias, showed reversal of atherosclerosis (Hackam, 2000).
A randomised, controlled trial showed a homocysteine reduction from 11.1 to 7.2 and a reduction in the rate of artery blocking after angioplasty. The number requiring further treatment was reduced by 50% (Schnyder, 2001).
A further trial with folic acid and B12 showed a reduction in abnormal ECGs on exercise (Vermeulen, 2000).
Other trials have shown increased artery flexibility with high dose folic acid, but this may be a pharmacological effect of folate rather than a homocysteine related effect.
How much B12 is enough?
How much B12 is enough?
To avoid elevated homocysteine blood B12 levels should be about 300 pmol/l or greater.
For meat-eaters to get blood B12 above 300 pmol/l requires about 3 m g (micrograms or mcg) per day.
As this is spread across several meals absorption will be about 50%, so an absorbed amount of 1.5 m g is required.
This can be obtained from:
- 3 m g per day from fortified foods consumed in several meals
- 10 m g per day from a single daily supplement
- 2000 m g per week from a single weekly supplement
(A similar analysis can be done for folate and shows a desirable blood level to be about 20 nmol/l, corresponding to about 400 m g per day, which is easily exceeded on a varied vegan diet.)
Vegan sources of B12
Claimed sources include:
- Tempeh (no effect)
- Nori (adverse effect if dried; neutral effect if raw)
- Spirulina (probable adverse effect)
- Klamath lake algae (no demonstrated or likely effect)
- Barley or wheat grass (no demonstrated or likely effect)
- Gut bacteria (no effect)
- Organic vegetables (no or minimal effect)
- Mushrooms (no or minimal effect)
- Dirt (little effect)
- Warm washed carrots (not a chance)
- Raw vs cooked food (no effect)
Practical sources include;
- Fortified foods
Much confusion has been caused by the use of test methods that cannot distinguish B12 from B12 analogues.
Some analogues are not absorbed but others compete with true B12 in the body making deficiency worse.
B12 and natural diet
B12 levels in primates
Wild primates show B12 levels over 220 pmol/l which fall within a few years in captivity to about 40 pmol/l when fed a hygienic plant based diet.
B12 sources in wild primates
A few primates have a second stomach similar to a cow's rumen. The rumen contains bacteria that produce B12 if the diet includes enough cobalt.
Many primates eat their own faeces and obtain B12 produced by bacteria in the lower intestine (too low for absorption).
All primates eat insects found on or in their normal diet and many deliberately seek out insects, e.g. chimps and termites.
None consume quantities of meat that would provide an adequate level of B12.
Our need for B12 has nothing to do with a need for meat.
Ultimately all B12, including that in meat and milk, comes from bacteria just as the B12 in supplements and fortified foods does.
Testing B12 levels
Blood B12 level
The measurement is unreliable if high levels of analogues are being consumed, e.g. from spirulina or seaweed as these fool the blood test while deficiency gets worse. Otherwise, blood levels above 300 pmol/l or 400 pg/ml indicate sufficient B12.
Only detects anaemia which is unlikely with high folate.
Blood homocysteine level
As the key functional measure, levels above about 12 m mol/l indicate a problem, but this may be due to any of:
- Inadequate B12 intake
- Inadequate folate intake
- Inadequate B6 intake
- Hypothyroidism (possibly due to inadequate iodine)
- Heavy consumption of unfiltered coffee
- Kidney problems
Blood or urine MMA level
Another key marker of inadequate B12. Doesn't dependent on other factors above apart from kidney problems, but not as strongly related to adverse effects. Levels should be less than 370 nmol/l in blood or <4m g/mg creatinine in urine.
B12 deficiency may have serious consequences, particularly for infants as onset is more rapid and lasting damage more common.
Good B12 intake may be the key to adding 4 years to vegan life-span and putting vegans clearly ahead of other groups in mortality comparisons.
It may also reduce risk of pregnancy complications, birth defects and dementia.
Adequate B12 can be obtained from:
- at least 3 micrograms per day from including fortified foods in several meals or
- at least 10 micrograms as a daily supplement or
- at least 2000 micrograms as a weekly supplement
Our need for B12 has nothing to do with a need for meat but is shared by most other primates who get B12 from dirt, insects and faeces containing B12 from bacteria. In our modern sanitised but polluted world B12 extracted from bacteria provides the most convenient and reliable source.
B12 is an essential part of a healthy vegan diet
Don't endanger your health by missing out
B12, folate and homocysteine levels
Germany 2002: Abstract 18, Loma Linda Conference on Vegetarian Nutrition, Cobalamin and homocysteine status of vegans - results of the German Vegan Study, Jochen Koschizke
Germany 2001: Clinical Chemistry, 2001; 47: 1094-1101, Total homocysteine, Vitamin B12, and total antioxidant status in vegetarians, Wolfgang Herrmann et al.
Italy 2002: Abstract 17, Loma Linda Conference on Vegetarian Nutrition, Effect of Vegetarian diet on the homocysteine levels, Riccardo Trespidi
Czechoslovakia 2000: Annals of Nutrition and Metabolism, 2000; 44: 135-138, Homocysteine levels in vegetarians versus omnivores, M. Krajcovicova-Kudlackova et al.
Chile 1999: Thrombosis and Haemostasis, 1999; 81: 913-7, Vegetarians and cardiovascular risk factors: hemostasis, inflammatory markers and plasma homocysteine, Diego Mezzano et al.
(plus reduction of homocysteine by B12 supplementation) Thrombosis Research, 2000; 100: 153-160, Cardiovascular risk factors in vegetarians: normalisation of hyperhomocysteinemia with vitamin B12 and reduction of platelet aggregation with n-3 fatty acids, Diego Mezzano et al.
Australia 1999: European Journal of Clinical Nutrition, 1999; 53: 895-899, The effect of diet on plasma homocysteine concentrations in healthy male subjects, NJ Mann et al.
Taiwan 2001: Journal of Nutrition, 2001; 132: 152-158, Plasma homocysteine levels in Taiwanese vegetarians are higher than those of omnivores, Chien-Jung Hung et al.
USA 1999:American Journal of Clinical Nutrition, 1999; 70: 586S-593S, Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians, Ella H Haddad et al.
Homocysteine and mortality
Israel: Annals of Internal Medicine, 1999; 131:321-330, Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem, Jeremy D Kark et al.
Norway: American Journal of Clinical Nutrition, 2001; 74: 130-136, Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study, Stein Emil Vollset et al.
USA: Archives of Internal Medicine, 1999; 15: 1077-1080, Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women, Andrew G Bostom et al.
Holland: Circulation, 2000; 101: 1506-1511, Hyperhomocysteinemia increases risk of death, especially in Type 2 diabetes, Ellen K Hoogeveen et al.
Vegetarian mortality and health
UK, USA and Germany 1999: American Journal of Clinical Nutrition, 1999; 70: 516S-524S, Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies, Timothy J Key et al.
UK 2002, Public Health Nutrition, 2002; 51: 29-36, Mortality in British vegetarians, Paul N Appleby et al.
Ireland 1993: Quarterly Journal of Medicine, 1993: 86: 703-708, Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects, P N Kirke et al.
Norway 2000: American Journal of Clinical Nutrition, 2000; 71: 962-968, Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine Study, Stein Emil Vollset et al.
Intervention trials with B vitamins
MRC, 1991: The Lancet, 1991; 338: 131-137, Prevention of neural tube defects: results of the Medical Research Council Vitamin Study.
Czeizel 1992:New England Journal of Medicine, 1992; 327: 1832-1835, Prevention of first occurrence of neural-tube defects by periconceptual vitamin supplementation, A E Czeizel and I Dudas.
Hackam 2000: American Journal of Hypertension, 2000; 13: 105-110, What levels of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of atherosclerosis in patients with homocyst(e)ine levels above and below 14 m mol/l, Daniel G Hackam et al.
Schnyder 2001: New England Journal of Medicine, 2001; 345: 1593-1600, Decreased rate of coronary restenosis after lowering of plasma homocysteine levels, Guido Schnyder et al.
Vermeulen 2000: The Lancet, 2000, 355: 517-522, Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial, E G J Vermeulen et al.
How much B12 is enough?
Annals of Internal Medicine, 1999; 131: 331-339, Serum total homocysteine concentrations in the third National Health And Nutrition Examination Survey (1991-1994): Population reference ranges and contribution of vitamin status to high serum concentrations, Jacob Selhub et al.
American Journal of Clinical Nutrition, 2000, 71: 514-522, Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring Study, Katherine L Tucker et al.
American Journal of Clinical Nutrition, 1987, 45: 671-678, Recommended dietary intakes (RDI) of vitamin B-12 in humans, Victor Herbert
B12 levels in primates
Personal communication with Monkey World Ape Sanctuary, April 2002
Primates of the World, Rod and Ken Preston-Mafham, 1999
General information on vegans and B12
Published Online: 31 Aug 2002