Vegetarian Diets and Homocysteine
Vitamin B12 deficiencies caused by vegetarian or vegan diets are just as devastating to adults as they are to infants and pregnant women. Vitamins technically are defined as “organic catalysts” – meaning that without their presence in our diets, our metabolic machinery slows, or is sufficiently damaged to eventually cause illness and disease. One of the most destructive changes in our bodies caused by vitamin B12 deficiency is the appearance of a toxic substance in our bloodstream known as homocysteine. Without sufficient dietary sources of vitamin B12, a chemical reaction within our bodies is impaired and causes blood concentrations of homocysteine to rise. Homocysteine is a toxin for almost every cell in our bodies, and increases the risk for birth defects, infertility, dementia, psychological illness, stroke, heart attacks, blood vessel disease, blood clots, osteoporosis and overall death rates. Worldwide studies of vegetarians and vegans show that the less animal food they eat, the higher are their blood concentrations of homocysteine.9, 21, 38, 60, 67, 70, 94, 101 Let’s take a look at how vegetarian diets raise blood concentrations of homocysteine and increase the risk for numerous diseases.
Homocysteine and Cardiovascular Disease
It is widely assumed that vegetarian diets reduce the risk for cardiovascular disease and heart attacks because they lower total and saturated fats in our diets. Unfortunately, this simplistic explanation is only part of the story. Total fat and saturated fat have been shown in large meta analyses to have negligible effect upon the atherosclerotic process that clogs the arteries and causes heart and blood vessel disease.143-146 In contrast, meta analyses published in the past 15 years have confirmed that homocysteine is an independent risk factor for cardiovascular disease and heart attacks.61, 130 The higher your blood levels of homocysteine, the greater will be your risk of having a stroke or heart attack. As I mentioned earlier, homocysteine is toxic to almost all cells in our bodies. It is particularly dangerous when high concentrations build up in our bloodstreams because it damages the cells lining blood vessels. This initial injury to the blood vessels represents one of the first steps in the artery clogging process. If blood concentrations of homocysteine remain high and the blood vessel damage goes on unabated for decades, it may result in fatal strokes and heart attacks. A recent (2008) meta analysis by Dr. Humphrey and colleagues indicated that for each (5 micromol/L) increase in blood homocysteine levels, the risk for cardiovascular disease events increased by approximately 20%.61
Because vegetarian diets cause vitamin B12 levels in the bloodstream to plummet, which in turn causes homocysteine levels to dangerously rise, you might expect to find high rates of cardiovascular disease in strict lifelong vegetarians. One of the problems in examining cardiovascular disease in vegetarians from the U.S. and Europe is that many of them aren’t strict vegetarians, and typically haven’t consumed vegetarian diets for their entire lives. All of these variables tend to confound the results of epidemiological studies. Given this scenario, what better place to examine vegetarian diets and than in India? With a population of 1.17 billion people, 31 % (362,700,000) of whom are vegetarians,42 India represents a country which can give us insight into study cardiovascular disease and plant based diets. As opposed to vegetarians in the U.S. and Europe, many Indian vegetarians are committed to lifelong vegetarian diets due to their religious convictions and family conventions.
If vegetarian diets provide protection from cardiovascular disease as the ADA suggests, then you might expect to find a low prevalence of heart disease and stroke in India because almost one third of its population are vegetarians. Unfortunately, this is not the case.137 In reality, the incidence of cardiovascular disease is much higher in India than in most other places in the world. Moreover, Indians develop cardiovascular disease at a much earlier age than people from other countries. In the largest study ever of 368 lifelong Indian vegetarians with cardiovascular disease, Dr. Kumar and co-workers showed that heart disease was higher in vegetarians and that they had lower blood levels of vitamin B12.79 I quote Dr. Kumar, “We believe that the beneficial effect of a vegetarian diet in this population is circumvented by deficiency of vitamin B12.”
Homocysteine and Neurological Diseases
Not only is homocysteine toxic to our blood vessels, but numerous studies also have found that it adversely affects brain function, behavior and mood.23, 129 People with higher blood concentrations of homocysteine have a greater risk for Alzheimer’s disease, dementia, depression, Parkinson’s disease and stroke. In a comprehensive 2010 review of 1,627 articles on high blood levels of homocysteine and vitamin B12 Dr. Werder133 concluded that: “Hyperhomocysteinemia (high blood levels of homocysteine) with or without hypovitaminosis B12 (low blood levels of vitamin B12) is a risk factor for dementia.” In addition to vitamin B12 deficiencies another B vitamin, folate, can cause blood concentrations of homocysteine to rise. However in a study involving 2,403 older people, Dr. Clarke and colleagues24 found that, “the relative importance of vitamin B12 deficiency as a determinant of homocysteine concentrations and cognitive impairment is probably greater than that of folate deficiency in older adults.” Additionally, a recent study by Dr. Selhub’s research group showed that high dietary intakes of folate seems to make B12 deficiencies worse by further increasing blood concentrations of homocysteine.114 This is precisely the dietary pattern found in the blood of most vegetarians – low B12 and adequate or elevated folate. Is it any wonder why so many vegetarians and vegans have dangerously high blood levels of homocysteine?
Homocysteine and Bone Disease
The list of chronic diseases associated with high blood concentrations of homocysteine seems almost endless and has recently been extended to bone disease. By raising blood homocysteine levels, vegetarian diets may not only increase your risk for neurological disorders and cardiovascular disease, but they also increase bone fracture risk. The notion that vegetarians have weaker bones than their meat eating counterparts was verified in the largest study ever undertaken in a vegetarian population (9,420 vegetarians and 1,126 vegans). The authors of the EPIC-Oxford study concluded that, “The higher fracture risk in the vegans appeared to be a consequence of their considerably lower mean calcium intake.”2 Low calcium and vitamin D intakes are well known risk factors for bone fractures and osteoporosis, and these nutritional deficiencies are common in vegan and vegetarian populations. But to add insult to injury, you can now add another strike against vegan and vegetarian diets in promoting bone disease. Since 2003, numerous studies have identified low B12, low folate or high homocysteine blood levels as risk factors for poor bone density, increased fractures, or osteoporosis.2, 4, 17, 34, 51, 53, 54, 58, 78, 82, 112, 125
Although we don’t completely understand how high blood levels of homocysteine adversely affect bone, tissue studies have identified a number of mechanisms. First homocysteine seems to impair the normal bone mineralization process.17 It also causes an accelerated breakdown of bone and inhibits the formation of new bone cells.51 Some of the best evidence implicating homocysteine in bone disease comes from human dietary interventions. In a two year study of 559 elderly women in Japan, Dr. Sato and fellow researchers showed that supplementation of vitamin B12 and folate reduced blood concentrations of homocysteine by 38%.112 But more importantly women in the vitamin supplemented group suffered 33 fewer hip fractures than women in the un-supplemented control group.
One of the best ways you can prevent hip fractures is to follow The Paleo Diet. Because you will be eating meat and fish at virtually every meal, you won’t have to worry about vitamin B12 deficiencies, as these two foods are our best sources of this essential vitamin. The other mainstay of The Paleo Diet is fresh fruit and veggies which are rich sources of the B vitamin, folate. The combination of lots of meat and fish along with plenty of fruits and vegetables at every meal will ensure that you do not develop vitamin B12 or folate deficiencies and that your blood homocysteine levels will remain low throughout your life – just as nature intended.
Homocysteine and Infertility
Before I leave homocysteine, I’ve got to cover one more topic that for some of you may be the most important revelation of all about this noxious molecule. By now, you know that elevated blood concentrations of homocysteine result primarily from too little vitamin B12 and folate in our diets. When adequate stores of these two B vitamins are present from nutritious foods in our diet (e.g. meats, fresh fruits and veggies), then our cells can defuse the poisonous effects of homocysteine and convert it into less toxic compounds. However, when B12 is lacking or deficient, as it almost always is in vegetarian and vegan diets, then homocysteine builds up in our bloodstream and literally infiltrates nearly every cell in our bodies.
Healthy egg cells in women and healthy sperm cells in men are absolutely essential requirements for getting pregnant, staying pregnant and producing normal embryos, vigorous infants and healthy children. I’ve previously outlined how vitamin B12 deficiencies can elevate blood levels of homocysteine and cause numerous adverse health problems in pregnant women, their unborn fetuses and nursing infants. In addition to these unfavorable effects, a diet deficient or marginal in vitamins B12 and folate can severely reduce your chances for successful fertilization and conception. Infertility is a huge problem in both the U.S. and elsewhere11, 122 and affects at least 6 million people in the U.S. or more importantly about 7.4% of the reproductive age population.119 Many environmental and genetic factors may be involved. However, one thing is certain, as a couple, if you or your partner’s blood levels of vitamin B12 and/or folate are low and your homocysteine is elevated, your chances for a normal conception and pregnancy will be significantly reduced.8, 12-14, 30, 36, 93, 98, 116, 128
The injurious effects of homocysteine in our bones and in our cardiovascular and nervous systems have been much better studied than in our reproductive systems. Nevertheless, it is becoming increasingly evident that the low vitamin B12 and folate status responsible for elevated homocysteine is toxic to both sperm and egg cells and may represent a major, previously unrecognized risk factor for infertility. More than 30 years ago, at least one group of researchers pointed out that Indian vegetarian men maintained lower vitamin B12 concentrations in their sperm than non-vegetarians and attributed these values to their vegetarian diet.65 Additionally, a number of these earlier studies hinted that vitamin B12 supplementation could improve sperm function and vigor and even boost male fertility.57, 65
If we fast forward to the 21st century, in the past five to ten years similar nutritional patterns have been discovered in western populations. In a recent (2009) study of 172 men and 223 women who were unable to conceive, 36% of men and 23% of women had vitamin B12 deficiencies. Almost 40% of the infertile men had abnormal semen that was directly related to their vitamin B12 deficiencies. Other recent studies in men show that low dietary folate and vitamin B12 are associated with high blood concentrations of homocysteine that likely underlie abnormal sperm function. On the flip side of the equation, women with compromised dietary B12 and folate intakes frequently have elevated blood levels of homocysteine68 which prevent them from becoming pregnant. We are not completely sure how these blood chemistry changes impede successful pregnancies in women, but tissue studies suggest that egg cells infiltrated by homocysteine and deficient in vitamin B12 and folate make them fragile and unable to continue with a normal pregnancy once fertilized.13, 126
Vegetarian Diets: Additional Fertility Problems
Menstrual Problems caused by Vegetarian Diets
In addition to B vitamin deficiencies and elevated blood concentrations of homocysteine, vegetarian diets are frequently associated with menstrual problems known to affect fertility. A total of five studies have compared the incidence of menstrual irregularities between vegetarians and meat eaters. Four out of these five studies demonstrated significantly higher rates of menstrual complications in vegetarians. Not all types of scientific experiments have equal clout in establishing cause and effect. Of the five studies, four were epidemiological (population) studies and one was an actual experimental intervention. Because dietary interventions represent the most powerful experimental procedure for determining if dietary changes improve health or cause illness, they carry more weight than epidemiological studies. Let’s take a look at the only dietary intervention investigating vegetarian diets on menstrual health.
Dr. Pirke and researchers at the University of Trier in Germany randomly divided 18 young women with normal menstrual periods into either vegetarian or non-vegetarian diet groups. After six weeks, 7 of the 9 women assigned to the vegetarian diet stopped ovulating, whereas only a single woman in the meat eating group experienced this problem.147 The results of this experiment are shocking. Within only six weeks of consuming a vegetarian diet, 78% of healthy, normally cycling women ceased ovulating. The takeaway: if you are trying to get pregnant, one of your best strategies is to avoid vegetarian diets. While you’re at it, make sure your husband or partner does the same.
Zinc Deficiencies Impair Sperm Function
One of the most frequent nutritional shortcomings of vegetarian and vegan diets is that they fall short of recommended intakes for zinc. In the largest epidemiological study ever of vegetarians (The EPIC-Oxford Study) Dr. Davey and colleagues noted that vegans had “…the lowest intakes of retinol [vitamin A], vitamin B12, vitamin D, calcium and zinc…” when compared to meat and fish eaters.31 More importantly, with zinc it’s not just how much is present in your food, but how much is actually absorbed in your body. Although dietary zinc intakes in vegetarian diets sometimes appear to be adequate on paper – in the body they actually result in deficiencies32, 44, 45, 62 because most of plant based zinc is bound to phytate and, therefore, unavailable for absorption. Phytate is an antinutrient found in whole grains, beans, soy and other legumes that prevents normal assimilation of many minerals. Laboratory experiments show that vegetarians only absorb about half as much zinc as meat eaters because zinc from animal food is much better assimilated than from plant foods.
Based upon this information, you might expect blood concentrations of zinc to be lower in vegetarians than meat eaters. Sometimes scientists have found this to be the case, but not always. The problem here has to do with where zinc ends up in our bodies after we ingest it. Most zinc finds its way into the interior of cells and does not accumulate in the liquid portion (plasma) of blood. Consequently, unless scientists examine zinc concentrations within cells, readings obtained in blood plasma frequently do not accurately reflect body stores of this essential mineral. In virtually every study of vegetarians which measured zinc levels inside various cells (red blood cells, hair cells and skin cells in saliva), plant based diets caused zinc deficiencies. In one study, 12 meat eating women were put on a lacto-ovo vegetarian diet, and after only 22 days Dr. Freeland-Graves and co-workers reported that zinc concentrations in the women’s salivary cells plunged by 27%.44 Similar results were described by Dr. Srikumar and colleagues from a longer term experiment in which 20 meat eating men and women adopted a lactovegetarian diet for an entire year.117 In this study, both hair cells and blood levels of zinc sharply declined and remained low throughout the 12 month experiment.
So, I’ve set the stage for zinc deficiencies and infertility problems. Because of their low zinc content and bioavailability, long term vegetarian diets almost always cause zinc deficiencies.20, 32, 44, 45, 62 Numerous studies have shown that infertile/subfertile men had poor seminal quality that was associated with vegetarian diets6, 65 or reduced zinc levels in their semen. Virtually every well controlled experimental study ever conducted shows that men put on zinc deficient diets ended up with reduced sperm counts, impaired sperm health and often depressed blood testosterone levels. The good news is that these deleterious changes in male reproductive function can be reversed if zinc rich diets (e.g. The Paleo Diet) are consumed, or if zinc pills are supplemented.136 Dr. Steegers-Theunissen’s research group in the Netherlands showed dramatic improvements in the reproductive health of 103 sub-fertile men when zinc and folic acid were supplemented.37 Following the six month supplementation program, sperm counts increased significantly in the sub-fertile men while sperm abnormalities declined by 4%. A similar study of 14 infertile men from India also indicated that zinc supplementation increased sperm health, sperm counts and shortly thereafter resulted in three successful conceptions by these men’s wives.123
Whether you are a man or woman, if you want to sidestep infertility problems, the best advice I can give you is to abandon vegetarian diets and adopt the nutritional patterns that have sustained our hunter gatherer ancestors for the past 2.6 million years. There are no known risks to adopting The Paleo Diet, and in fact, regular consumption of meat, seafood and fresh fruit and vegetables at the expense of cereals, dairy and processed foods will prevent vitamin B12 and folate deficiencies. In turn these essential vitamins will ensure that your blood levels of homocysteine will return to normal – effectively reducing your risk for cardiovascular, neurological, bone and reproductive diseases.
In Vegetarian and Vegan Diets: Nutritional Disasters Part 3 we’ll discuss the additional copious shortcomings of vegetarian and vegan diets and why The Paleo Diet is optimal for health and wellbeing.
Loren Cordain, Ph.D., Professor Emeritus
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